UCL Cancer Institute


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6 October 2014; 6pm Monday

Special Seminar: Professor Hilary Calvert Retirement Lecture

Calvert Special Seminar - 6pm Monday - 6th October

Wilkins Gustave Tuck Lecture Theatre (Map)

Professor Hilary Calvert
In search of the Achilles Heels of Cancers: reflections on a misspent career

Professor Hilary Calvert has had an outstanding career spanning over 40 years. He has made substantial advances in research and anti-cancer drug development and his clinical commitment has led to innovative and lasting contributions that continue to benefit patients today.

Followed by a reception in the Courtyard Café, Paul O'Gorman Building

All are welcome

 




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25 September 2014

UCL Cancer Institute achieved the Athena Swan Silver Award !

Athena Swan Under the leadership of Professor Kerry Chester the Institute has been successful in achieving Silver Athena SWAN status.

The awards, announced today, recognise commitment to advancing women's careers in science, technology, engineering, maths and medicine in higher education and research.

Seven institutions, including two research institutes, achieved their first ever Athena SWAN award in the first of two awards rounds this year. Overall, 83 higher education institutions, research institutes and individual schools and departments will receive awards.

The University College London - UCL Cancer Institute achieved a prestigious Silver department award.

Click here to see the Athena Swan 2014 results.

 




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16 January 2014

Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution

Published in: Cancer Discovery (Online).


Dewhurst SM, McGranahan N, Burrell RA, Rowan AJ, Grönroos E, Endesfelder D, Joshi T, Mouradov D, Gibbs P, Ward RL, Hawkins NJ, Szallasi Z, Sieber OM, Swanton C.

Pubmed: http://www.ncbi.nlm.nih.gov/pubmed/24436049

ChesterThe contribution of whole-genome doubling to chromosomal instability (CIN) and tumor evolution is unclear. We use long-term culture of isogenic tetraploid cells from a stable diploid colon cancer progenitor to investigate how a genome-doubling event affects genome stability over time. Rare cells that survive genome doubling demonstrate increased tolerance to chromosome aberrations. Tetraploid cells do not exhibit increased frequencies of structural or numerical CIN per chromosome. However, the tolerant phenotype in tetraploid cells, coupled with a doubling of chromosome aberrations per cell, allows chromosome abnormalities to evolve specifically in tetraploids, recapitulating chromosomal changes in genomically complex colorectal tumors. Finally, a genome-doubling event is independently predictive of poor relapse-free survival in early-stage disease in two independent cohorts in multivariate analyses [discovery data: hazard ratio (HR), 4.70, 95% confidence interval (CI), 1.04-21.37; validation data: HR, 1.59, 95% CI, 1.05-2.42]. These data highlight an important role for the tolerance of genome doubling in driving cancer genome evolution.



Original research article can be found at: http://cancerdiscovery.aacrjournals.org/content/early/2014/01/14/2159-8290.CD-13-0285.long

 

See also: Editorial in New Scientist 

 



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6 October 2013

Women with recurrent ovarian cancer survive longer after treatment with cediranib

Presented at: the 2013 European Cancer Congress (ECC2013) ( Online).


Professor Jonathan Ledermann


Abstract no: LBA10. “Randomised double-blind phase III trial of cediranib (AZD 2171) in relapsed platinum sensitive ovarian cancer: Results of the ICON6 trial”. Presidential session III, 12.30 hrs CEST, Monday 30 September, Hall 7.1.


Women with ovarian cancer that has recurred after chemotherapy have survived for longer after treatment with a biological therapy called cediranib, according to new results to be presented today (Monday) at the 2013 European Cancer Congress (ECC2013).

ledermanOct2013 Cediranib, which is taken in pill form, is an inhibitor of a cell signalling process involved in formation of tumour blood vessels, essential for tumour growth, and it is the first oral inhibitor of its kind to show an improvement in the time before patients' disease progresses and in overall survival. The drug is a tyrosine kinase inhibitor, a type of biological therapy that blocks vascular endothelial growth factor (VEGF) receptors, which control the development of blood vessels required for growing tumours.

Professor Jonathan Ledermann, Professor of Medical Oncology at UCL Cancer Institute, University College London, presented first results from ICON6, an international randomised, double-blind, academic clinical phase III trial of cediranib.

"In women whose ovarian cancer had been treated with platinum-based chemotherapy together with cediranib given during and after the chemotherapy, we found that the time before the tumour started to grow again was extended by an average of 3.2 months. This sounds like a modest increase but represents about a 30% improvement, with overall survival also increased by a similar amount, to an average of 2.7 months over a two-year period of follow-up," he said.

Studies with chemotherapy alone have shown that the time before patients experience disease progression following treatment for a relapse that is sensitive to platinum-based chemotherapy is an average of eight to nine months. These latest results show that cediranib in addition to chemotherapy increased the time before the disease progressed from 9.4 to 12.6 months over a period of two years, and it extended overall survival from 17.6 to 20.3 months.

"These are ground-breaking data," said Prof Ledermann. "Cediranib is the first oral VEGF tyrosine kinase inhibitor that has been shown to delay tumour progression and improve overall survival in recurrent ovarian cancer. It is simple to give for a prolonged period and in most patients it is well-tolerated." Adverse side-effects included high blood pressure, diarrhoea and fatigue.

A total of 456 patients whose ovarian cancer had recurred were enrolled in the trial in 63 centres from the UK, Canada, Australasia and Spain. They were randomised to receive platinum-based chemotherapy together with a placebo (the reference arm of the trial), or 20 mg a day of cediranib during chemotherapy followed by placebo for 18 months (concurrent arm of the trial), or 20 mg a day of cediranib during chemotherapy followed by cediranib as a maintenance treatment (maintenance arm).

"ICON6 has a three-arm design in which the effect of cediranib given with chemotherapy and continued as maintenance can be compared with standard chemotherapy. This is the first trial to have demonstrated a benefit of concurrent cediranib with chemotherapy, as well as demonstrating an additional benefit with maintenance cediranib," he said.

An increased survival time of nearly three months is significant in this group of patients. Prof Ledermann explained: "In previous ovarian cancer trials any improvement seen with each new treatment has been incremental. Survival has improved through sequential use of drugs. Most of the recent positive trials have shown an improvement in progression-free survival. Trials showing an improvement in overall survival are uncommon. Cediranib produces an incremental improvement in progression-free survival and an incremental improvement in overall survival. Although the average improvement in overall survival is 2.7 months, some patients will see a much more substantial benefit."

ECCO president, Professor Cornelis van de Velde, commented: "These are important results for women with recurrent ovarian cancer. Once the disease has recurred there are few treatment options available that make a significant difference to its progression and to overall survival. The ICON6 trial shows that cediranib does make a difference and it is to be hoped that it can be made available to women as soon as is practicable."

SOURCE European CanCer Organisation (ECCO)

    



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24 July 2013

Foot and Mouth Disease Virus used to target Cancer

Published in: Plos One 2013 ( Online).


Kogelberg* H, Miranda* E, Burnet J, Ellison D, Tolner B, Foster J, Picón C, Thomas GJ, Meyer T, Marshall JF, Mather SJ and Chester K
*These authors contributed equally to this work !

PLoS One. 2013 Sep 4;8(9):e73260. doi: 10.1371/journal.pone.0073260.

Scientists at the UCL Cancer Institute working to develop treatments for cervical cancer have harnessed a part of the foot-and-mouth disease virus to create a genetically engineered antibody fragment designed to target cancer. The work, sponsored by the ‘Debbie Fund’ (www.debbiefund.org) and published today in the international open access journal PLOS ONE, showed that the new antibody reduced cancer cell migration, was able to target radioactivity to solid tumours and was internalised into cancer cells. This therefore has implications for the spread of cancer and could provide a new route for delivering targeted treatment.

Chester Researchers at the UCL Cancer Institute worked in collaboration with teams at The Barts Cancer Institute and Southampton Cancer Research UK to produce the new antibody which will be manufactured in yeast cells. It binds to the avß6 integrin, a protein that promotes tumour activity.

Professor Chris Boshoff, Director of the UCL Cancer Institute, commented: “The results of this research show promise for a range of potential applications in imaging, function blocking or targeted delivery of therapeutic agents within cancer treatment”.

“This new antibody brings us an important step closer to a new treatment for patients with cervical cancers” said Kerry Chester, Professor of Molecular Medicine, and one of the lead investigators of the Debbie Fund project.

The Debbie Fund was set up in memory of Debbie Phillips, who died of cervical cancer in 2010. During the progression of Debbie’s disease, her family and friends discovered that worldwide there was no dedicated research into a drug treatment specifically for cervical cancer and the fund was established to raise finance for this essential research. The Debbie Fund is also supporting further studies at the UCL Cancer Institute, using advanced DNA sequencing technologies and functional screens to decipher and exploit the genetic code of cervical cancer for the development of improved treatments.

Clinical experts Dr Mary McCormack and Professor Tim Meyer commented: “There is an urgent need to develop new and better therapies for patients with cervical cancer, so the innovative approaches which Debbie Fund is supporting are extremely important in potentially improving outcomes for patients in the future.”

The research was also supported by Cancer Research UK, the Experimental Cancer Medicine Centre, UCL Cancer Institute Research Trust and NIHR.

Original research article can be found at: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0073260

    



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24 July 2013

Meta-analysis of IDH-mutant cancers identifies EBF1 as an interaction partner for TET2

Published in: Nat Commun. 2013 ( Online).


Guilhamon P, Eskandarpour M, Halai D, Wilson GA, Feber A, Teschendorff AE, Gomez V, Hergovich A, Tirabosco R, Fernanda Amary M, Baumhoer D, Jundt G, Ross MT, Flanagan AM, and Beck S.
Nat Commun. 2013 Jul 17;4:2166. doi: 10.1038/ncomms3166.

Cancer is a disease of the genome caused predominantly by mutations and epimutations (changes to the chemical marking of the DNA rather than the sequence itself). By comparing such epimutations in cancers with and without specific mutations, Guilhamon and colleagues discovered a novel targeting mechanism explaining why certain genes are more affected in the mutant cancers.

Abstract

Beck Isocitrate dehydrogenase (IDH) genes 1 and 2 are frequently mutated in acute myeloid leukaemia (AML), low-grade glioma, cholangiocarcinoma (CC) and chondrosarcoma (CS). For AML, low-grade glioma and CC, mutant IDH status is associated with a DNA hypermethylation phenotype, implicating altered epigenome dynamics in the aetiology of these cancers. Here we show that the IDH variants in CS are also associated with a hypermethylation phenotype and display increased production of the oncometabolite 2-hydroxyglutarate, supporting the role of mutant IDH-produced 2-hydroxyglutarate as an inhibitor of TET-mediated DNA demethylation. Meta-analysis of the acute myeloid leukaemia, low-grade glioma, cholangiocarcinoma and CS methylation data identifies cancer-specific effectors within the retinoic acid receptor activation pathway among the hypermethylated targets. By analysing sequence motifs surrounding hypermethylated sites across the four cancer types, and using chromatin immunoprecipitation and western blotting, we identify the transcription factor EBF1 (early B-cell factor 1) as an interaction partner for TET2, suggesting a sequence-specific mechanism for regulating DNA methylation.

    



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7 July 2013

In vivo imaging of glucose uptake and metabolism in tumors

Published in: Nat Med. 2013 ( Online).


Walker-Samuel S, Ramasawmy R, Torrealdea F, Rega M, Rajkumar V, Johnson SP, Richardson S, Gonçalves M, Parkes HG, Arstad E, Thomas DL, Pedley RB, Lythgoe MF, and Golay X.
Nat Med. 2013 Jul 7. doi: 10.1038/nm.3252.

Golay Sugar makes cancer light-up in MRI scanners A new technique for detecting cancer by imaging the consumption of sugar with magnetic resonance imaging (MRI) has been unveiled by UCL scientists. The breakthrough could provide a safer and simpler alternative to standard radioactive techniques and enable radiologists to image tumours in greater detail.

The new technique, called ‘glucose chemical exchange saturation transfer’ (glucoCEST), is based on the fact that tumours consume much more glucose (a type of sugar) than normal, healthy tissues in order to sustain their growth.

The researchers found that sensitising an MRI scanner to glucose uptake, caused tumours to appear bright on MRI images of mice.

Lead researcher Dr Simon Walker-Samuel, from the UCL Centre for Advanced Biomedical Imaging (CABI) said: “GlucoCEST uses radio waves to magnetically label glucose in the body. This can then be detected in tumours using conventional MRI techniques. The method uses an injection of normal sugar and could offer a cheap, safe alternative to existing methods for detecting tumours, which require the injection of radioactive material.”

Professor Mark Lythgoe, Director of CABI and a senior author on the study, said: “In principal, we can detect cancer using the equivalent amount of sugar as found in half a standard sized chocolate bar.

“MRI uses standard imaging technology available in many large hospitals,” he continued. “Our research reveals a useful and cost-effective method for imaging cancers. In the future, patients could potentially be scanned in local hospitals, rather than being sent for referrals to specialist medical centres.”

According to UCL’s Professor Xavier Golay, another senior author on the study: “Our cross disciplinary research could allow vulnerable patient groups such as pregnant women and young children to be scanned more regularly, without the risks associated with a dose of radiation.”

The study has been published in the journal Nature Medicine and trials are now underway to detect glucose in human cancers. Dr Walker-Samuel added: “We have developed a new state-of-the-art imaging technique to visualise and map the location of tumours that will hopefully enable us to assess the efficacy of novel cancer therapies.”

This work was supported by public and charitable funding from the Department of Health’s NIHR Biomedical Research Centres funding scheme, Cancer Research UK, Engineering and Physical Sciences Research Council (EPSRC) and the British Heart Foundation (BHF).

    



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16 June 2013

The genetics of chondrosarcoma – a novel link with a gene related to the production of cartilage – COL2A1

Published in: Nat Genet. 2013 ( Online).


Tarpey PS, Behjati S, Cooke SL, Van Loo P, Wedge DC, Pillay N, Marshall J, O'Meara S, Davies H, Nik-Zainal S, Beare D, Butler A, Gamble J, Hardy C, Hinton J, Jia MM, Jayakumar A, Jones D, Latimer C, Maddison M, Martin S, McLaren S, Menzies A, Mudie L, Raine K, Teague JW, Tubio JM, Halai D, Tirabosco R, Amary F, Campbell PJ, Stratton MR, Flanagan AM, Futreal PA.
Nat Genet. 2013 Jun 16. doi: 10.1038/ng.2668 [Epub ahead of print]


Abstract

Flan Researchers from UCL Cancer Institute, The Wellcome Trust Sanger Institute and the Royal National Orthopaedic Hospital screened the functioning regions of the genome in 49 patients with chondrosarcoma. They found that mutations in the gene COL2A1, a gene central to the production of cartilage, played a role in cancer development in almost 40 per cent of the patients.

COL2A1 is the gene for a type of collagen. Collagens are fibrous proteins that are responsible for the tensile strength of bone, cartilage and other tissues. This collagen is particularly important for the development of cartilage and thus the gene is very active in cartilage cells. This is the first time that a collagen gene has been shown to be involved in the development of a cancer. The team speculates that the high activity of COL2A1 in cartilage cells could contribute to the formation of mutations that underlie the development of chondrosarcoma.

The team also uncovered the Indian Hedgehog pathway that contributes to the development of this bone cancer in one in five patients with the disease. Drugs that inhibit this pathway already exist, and therefore the team's finding offers potential new treatment options for many patients with this cancer type.

Chondrosarcoma is a cancer of cartilage and is the second most common type of primary bone cancer. The main treatment option is surgery as chemotherapy or traditional radiotherapy provides no significant benefit for patients with this disease. This study offers new approaches to diagnosing this tumour and possible new treatments.

The team looked at the activity of COL2A1 in other bone cancers but did not find mutations. The high frequency of mutation in COL2A1 in chondrosarcoma patients could therefore become a diagnostic marker to differentiate it from other bone cancers.

    



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Monday 24 June 2013

UCL Cancer Institute – SPECIAL SEMINAR
5pm, Monday 24th June 2013
J Z Young Lecture Theatre, Anatomy Building – entrance off Gower Street (location)



The Hippo-YAP pathway in organ size control and tumorigenesis

Professor Kun-Lianag Guan, University of California, San Diego.


Prof. Kun-Liang Guan has a long standing interest in understanding mammalian signal transduction cascades. His research mainly focuses on signal transduction mechanisms regulating cell growth and organ size. While researching the roles of the TSC-mTOR pathway in cell size control and nutrient signalling by studying biosynthesis and autophagy he has also over the past 5 years made ground breaking discoveries in the Hippo tumour suppressor signalling field. His laboratory has described how Hippo signalling controls the proto-oncoproteins YAP/TAZ by spatial (nucleo-cytoplasmic shuttling) and temporal (protein stability) regulatory mechanisms, in addition to establishing that Hippo signalling is regulated by cell attachment, cell-cell contacts as well as G-protein coupled receptor (GPCR) signalling. He has published influential papers in highly ranked peer-reviewed journals, thereby establishing key roles of Hippo signalling in stem cell and cancer cell biology. Here, Prof. Guan, who is adjunct professor at the universities of Michigan, Fudan and Zhejiang in addition to his post at the University of California, will focus on presenting recent progress in Hippo signalling, a novel intracellular signal transduction cascade in control of cell death, proliferation and differentiation.

Host: Alexander Hergovich (a.hergovich@ucl.ac.uk)

More information on Prof. Kun-Liang Guan and his research can be found at:
http://en.wikipedia.org/wiki/Kun-Liang_Guan
http://biomedsci.ucsd.edu/faculty/faculty_descrip.aspx?id=226


Selected publications over the past years:
Yu, F.X., et al. Genes Dev. 2013 Jun 1;27(11):1223-32.
Russell, R.C., et al. Nat Cell Biol. 2013 May 19. doi: 10.1038/ncb2757.
Zhao, D., et al. Cancer Cell. 2013 Apr 15;23(4):464-76.
Kim, J., et al. Cell. 2013 Jan 17;152(1-2):290-303.
Tumaneng, K., et al. Nat Cell Biol. 2012 Dec;14(12):1322-9.
Mo, J.S., et al. Genes Dev. 2012 Oct 1;26(19):2138-43.
Yu, F.X., et al. Cell. 2012 Aug 17;150(4):780-91.
Xiao, M., et al. Genes Dev. 2012 Jun 15;26(12):1326-38.
Lian, I., et al. Genes Dev. 2010 Jun 1;24(11):1106-18.
Zhao, S., et al. Science. 2010 Feb 19;327(5968):1000-4.
Zhao, B., et al. Genes Dev. 2010 Jan 1;24(1):72-85.
Mori, H., et al. Cell Metab. 2009 Apr;9(4):362-74.
Kim, E., et al. Nat Cell Biol. 2008 Aug;10(8):935-45.
Zhao, B., et al. Genes Dev. 2008 Jul 15;22(14):1962-71.
Zhao, B., et al. Genes Dev. 2007 Nov 1;21(21):2747-61.
Inoki, K., et al. Cell. 2006 Sep 8;126(5):955-68.

Full publication list:
http://www.ncbi.nlm.nih.gov/pubmed/?term=guan+kl

All are welcome. A reception will be held after the seminar in the Courtyard Café, Paul O’Gorman Building.


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Tuesday 28 May 2013

Tyrosine Kinase BMX Phosphorylates Phosphotyrosine-Primed Motif Mediating the Activation of Multiple Receptor Tyrosine Kinases

Published in: Science Signaling, May 28, 2013 (Online).


S. Chen*, X. Jiang*, C. A. Gewinner*, J. M. Asara, N. I. Simon, C. Cai, L. C. Cantley, S. P. Balk
*Authors contributed equally to this work

Sci. Signal. 6, ra40 (2013), pp.1-11


scinece Key points:

The Tec family tyrosine kinase BMX (bone marrow tyrosine kinase gene on chromosome X) is broadly expressed and activated downstream of phosphatidylinositol-3 kinase (PI3K) and SRC, but its substrates are unknown. Positional scanning peptide library screening with which the optimal phosphorylation motif of kinases can be determined, revealed a marked preference of BMX for a priming phosphotyrosine (pY) in the -1 position (the amino acid before the BMX phosphorylation site). This indicates that BMX substrates may include multiple tyrosine kinases with kinase domain pYpY sites required for full activity.

We found that BMX phosphorylated Y577 in the focal adhesion kinase (FAK) subsequent to Y576 phosphorylation by SRC. Further, we demonstrated that BMX loss using RNAi technology or Bmx-/- murine embryonic fibroblasts (MEFs) lead to markedly impaired FAK activity proving the direct involvement of BMX phosphorylation in FAK activity. In addition, we identified that insulin receptor (IR) phosphorylation at the kinase domain (Y1189/1190 and Y1185 sites) and downstream serine/threonin kinase AKT Thr308 phosphorylation, were similarly impaired by BMX loss.
However, AKT S473 phosphorylation in response to insulin was not impaired. These findings show that BMX, through its novel pYpY substrate motif functions as a central regulator linking signalling pathways mediated by PI3K, SRC, and multiple tyrosine kinases.

    



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Saturday, 1 June 2013

Relapsed Serous Ovarian Cancer: New Data Presented at ASCO


asco2013



A retrospective subgroup analysis of a Phase II study (Study 19) shows the effect that an investigational drug, olaparib, has on progression-free survival (PFS) compared with placebo in platinum-sensitive relapsed serous ovarian cancer patients with BRCA mutations.

Study 19 was a randomized, double-blinded Phase II clinical trial evaluating the efficacy and safety of olaparib 400mg twice daily maintenance therapy compared with placebo in 265 platinum-sensitive, relapsed, high grade serous ovarian cancer patients who had received two or more previous platinum regimens and who were in a partial or complete response following their last platinum-containing regimen. The primary endpoint was PFS. Results from the full study population, first presented at American Society of Clinical Oncology (ASCO) 2011 and later published in the New England Journal of Medicine (NEJM) in 2012, showed that olaparib maintenance therapy significantly extended PFS compared with placebo (HR=0.35; 95% CI 0.25--0.49 P<0.001, median PFS 8.4 vs. 4.8 months), however an interim overall survival (OS) analysis did not detect a benefit for olaparib compared with placebo (HR=0.94; 95% CI, 0.63 -- 1.39 P<0.75).

The initial pre-planned subgroup analysis of PFS and OS in patients with a BRCA mutation suggested an improved outcome compared to the overall study population. However, mutation status was known for only a minority of patients in the study (36.6%) at that time and additional biomarker work was therefore conducted to further investigate this signal. BRCA mutation status was subsequently determined for patients from either blood samples (taken pre-randomization) and/or archival tumor samples and BRCA mutation status was eventually documented for 254 (96%) of the 265 patients in Study 19 confirming that 136 (51%) patients in the study had a BRCA mutation (BRCAm).

Retrospective results, in the total BRCAm population showed that olaparib maintenance therapy prolonged PFS compared with placebo (HR 0.18; 95% CI 0.11-0.31; p<0.00001, median PFS 11.2 vs 4.3 months). This result was statistically significant. A second interim analysis of OS for olaparib (58% maturity) in the BRCAm group did not demonstrate a statistical significant difference between the two arms. A numerical advantage on the olaparib arm compared with placebo was observed (HR 0.74; 95% CI 0.46-1.19, p=0.21; median OS 34.9 mo vs. 31.9 mo). 23% of the BRCAm patients who received placebo (14/62) subsequently received a PARP inhibitor, potentially confounding the OS data in this subgroup.

The most common adverse reactions occurring more frequently in the BRCAm patients treating with olaparib were low grade nausea, fatigue, vomiting and anemia, similar to those seen in patients without BRCA mutations.

Jonathan Ledermann, MD, UCL Cancer Institute, University College London and lead study investigator, said: "These are encouraging results for patients with ovarian cancer who carry a BRCA mutation. The statistically significant seven month difference in progression-free survival in the subgroup of patients with a BRCA mutation supports the hypothesis that a personalized therapeutic approach based on BRCA mutation status could preferentially benefit this patient population. This warrants further investigation of olaparib in a Phase III clinical trial."

BRCA are human genes that belong to a type of genes known as tumor suppressors. Mutation of these genes has been linked to hereditary breast and ovarian cancer and a woman's risk of developing breast and/or ovarian cancer is greatly increased if she inherits a BRCA1 or BRCA2 mutation. Only 15% of ovarian cancers are found before the cancer has spread outside the ovary. Despite advances in treatment and diagnosis, for patients with ovarian cancer that has spread beyond the ovary, the 5-year survival rate is well below 50%.

As a result of these Phase II data, AstraZeneca has announced that it is developing Phase III clinical trial program to further evaluate olaparib in BRCA mutated ovarian cancer. AstraZeneca has submitted a Letter of Intent to file for approval with the European Medicines Agency for olaparib in ovarian cancer patients with BRCA mutations.

Jane Robertson, Global Product Vice President for olaparib at AstraZeneca, said: "We are committed to conducting further studies of olaparib in patients with BRCA mutated tumors and to assessing its full potential in these and other cancers. We look forward to continuing to work with our collaborators and partners to strengthen our understanding of which patients are likely to benefit most from olaparib through a program of translational science and pre-clinical research."

Original publication in:
The Wall Street Journal

References:
Ledermann et al. ASCO 2013 - Abstract 5505. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer (SOC) and a BRCA mutation (BRCAm); J Clin Oncol 31, 2013 (suppl; abstr 5505); 2013 ASCO Annual Meeting.

  



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Monday, 20 May 2013

Runners take on London Marathon to raise money for the UCL Cancer Institute


lonmar2013



11 runners took on the 26.2 miles of the London Marathon on 21st April, the warmest weekend of the year after having trained through some of the coldest spring conditions we’ve had in 100 years!

The runners were raising money for the UCL Cancer Institute Research Trust, the charity which supports the work of the UCL Cancer Institute by funding core equipment, building projects and other vital research taking place. 2 runners ran to raise money for specific causes, the Debbie Fund – which supports research into cervical cancer in the team headed by Professor Kerry Chester, and for Chordoma UK, a fund raising money for Professor Adrienne Flanagans research into this rare cancer.

The runners all completed the race with 5 runners finishing in less than 4 hours which is an outstanding achievement. The runners have raised in total more than £28,000, with money still being donated, which will be allocated to projects within the Institute.

Chairman Richard Sutton-Mattocks said, “We would like to thank all of our runners for the hard work and dedication they showed both in training and running the marathon and in fundraising for the charity. The UCL Cancer Institute Research Trust is a small charity which is dedicated to supporting the work of the research teams at the UCL Cancer Institute. The money raised by these runners and their supporters allows the charity to invest further in the cutting edge work the Institute is renowned for.”

If you would like to know more about the work of the UCL Cancer Institute Research Trust, please visit: the UCL Cancer Trust Homepage

  



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Monday, 6 May 2013

Genetic profile testing to improve NHS cancer care


Full detail here

dna Cancer patients across England will soon be offered a new type of gene testing on the NHS that should help doctors tailor their treatment better.

Scientists know that hundreds of different genes are linked to cancer, and they are learning how to test to find out which particular genes are involved, so they can target those particular mutations with the most appropriate treatments. Science and Medical Editor Lawrence McGinty reports.



A microchip test developed by scientists at University College Hospital (UCL) in London analyses 35 different genetic mutations linked to cancer, which then enables doctors to identify and target those particular genes.

Professor Charles Swanton from UCL said the test will enable NHS patients to receive better tailored cancer care.

" The future is being able to do many gene tests on a small amount of tissue, and what we are seeing is the beginning of that type of technology impacting on the future on NHS care. "

itv_video

  



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Monday 22-April 2013

UCL Cancer Institute-led study defines standard of care for non-Hodgkin lymphoma from the CR-UK UCL Clinical Trials Centre

Published in: The Lancet, April 22, 2013 (Online).


David Cunningham, Eliza A Hawkes, Andrew Jack, Wendi Qian, Paul Smith, Paul Mouncey, Christopher Pocock, Kirit M Ardeshna, John A Radford, Andrew McMillan, John Davies, Deborah Turner, Anton Kruger, Peter Johnson, Joanna Gambell and David Linch

Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles.


nature Background

Dose intensification with a combination of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) every 2 weeks improves outcomes in patients older than 60 years with diffuse large B-cell lymphoma compared with CHOP every 3 weeks. We investigated whether this survival benefit from dose intensification persists in the presence of rituximab (R-CHOP) in all age groups.

Methods

Patients (aged =18 years) with previously untreated bulky stage IA to stage IV diffuse large B-cell lymphoma in 119 centres in the UK were randomly assigned centrally in a one-to-one ratio, using minimisation, to receive six cycles of R-CHOP every 14 days plus two cycles of rituximab (R-CHOP-14) or eight cycles of R-CHOP every 21 days (R-CHOP-21). R-CHOP-21 was intravenous cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1·4 mg/m2 (maximum dose 2 mg), and rituximab 375 mg/m2 on day 1, and oral prednisolone 40 mg/m2 on days 1—5, administered every 21 days for a total of eight cycles. R-CHOP-14 was intravenous cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 2 mg, rituximab 375 mg/m2 on day 1, and oral prednisolone 100 mg on days 1—5, administered every 14 days for six cycles, followed by two further infusions of rituximab 375 mg/m2 on day 1 every 14 days. The trial was not masked. The primary outcome was overall survival (OS). This study is registered, number ISCRTN 16017947.

Findings

1080 patients were assigned to R-CHOP-21 (n=540) and R-CHOP-14 (n=540). With a median follow-up of 46 months (IQR 35—57), 2-year OS was 82·7% (79·5—85·9) in the R-CHOP-14 group and 80·8% (77·5—84·2) in the R-CHOP-21 (standard) group (hazard ratio 0·90, 95% CI 0·70—1·15; p=0·3763). No significant improvement was noted in 2-year progression-free survival (R-CHOP-14 75·4%, 71·8—79·1, and R-CHOP-21 74·8%, 71·0—78·4; 0·94, 0·76—1·17; p=0·5907). High international prognostic index, poor-prognosis molecular characteristics, and cell of origin were not predictive for benefit from either schedule. Grade 3 or 4 neutropenia was higher in the R-CHOP-21 group (318 [60%] of 534 vs 167 [31%] of 534), with no prophylactic use of recombinant human granulocyte-colony stimulating factor mandated in this group, whereas grade 3 or 4 thrombocytopenia was higher with R-CHOP-14 (50 [9%] vs 28 [5%]); other frequent grade 3 or 4 adverse events were febrile neutropenia (58 [11%] vs 28 [5%]) and infection (125 [23%] vs 96 [18%]). Frequencies of non-haematological adverse events were similar in the R-CHOP-21 and R-CHOP-14 groups.

Interpretation

R-CHOP-14 is not superior to R-CHOP-21 chemotherapy for previously untreated diffuse large B-cell lymphoma; therefore, R-CHOP-21 remains the standard first-line treatment in patients with this haematological malignancy. No molecular or clinical subgroup benefited from dose intensification in this study.

    



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Monday, 15 April 2013

BioMarin Licenses Factor VIII Gene Therapy Program for Hemophilia A From University College London and St. Jude Children's Research Hospital


Professor Amit Nathwani AN RAFAEL, Calif., Feb. 21, 2013 (GLOBE NEWSWIRE) -- BioMarin Pharmaceutical Inc. (Nasdaq:BMRN) announced that it has licensed a Factor VIII gene therapy program for hemophilia A from University College London (UCL) and St. Jude Children's Research Hospital. The company expects to select a development candidate this year, initiate and complete IND-enabling toxicology studies next year and initiate proof of concept human studies by the end of 2014. The license and commitment to support the research program was made possible by UCL Business, UCL's wholly-owned technology transfer company, working with Professor Amit Nathwani of the UCL Cancer Institute.

"Gene therapy is emerging as a powerful and viable way to treat genetic disorders and is complementary to our current suite of commercial products and research programs," said Jean-Jacques Bienaimé, Chief Executive Officer of BioMarin. "Hemophilia is an attractive target for gene therapy as factor levels in the blood serve as good biomarkers, relatively low factor levels are required for a clinically important benefit in severe patients and the current standard of care of intravenous infusions three times a week is quite onerous. We remain committed to maintaining a rich pipeline with the goal of filing an IND every twelve to eighteen months."

Detail at: BioMarin Pharmaceutical Inc. Press releases

    



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Sunday, 16 June 2013

Not Just a Walk in the Park for the UCL Cancer Institute


dogs Cure Cancer @ UCL Charity (Registered Charity No 1141310) would like to invite you to join us and Dima Yeremenko with the Good Boy Dog School to take your pet on a beautiful stroll around Kensington Gardens with his performing dogs.

It’s simple to sign up – and £15 per person, children go FREE.
Please purchase your tickets online (http://www.eventbrite.co.uk/event/5846644471)
Registration will be at 10.30 am and the walk will leave the Buckhill Shelter in Kensington Gardens* promptly at 11.00 so please don't be late.

As well as enjoying the walk you will be helping to raise money for the Cure Cancer @ UCL (www.curecancer-ucl.org) where the money raised will go directly to purchase much needed medical research equipment at the UCL Cancer Institute in our quest to find a cure for cancer.

Refreshments will be provided at the end of the walk by Company of Cooks at the Lido and each dog will receive a goodie bag of dog treats and training snacks provided by Husse the International super-premium pet food company.

Dima and the Good Boy Dog School team will be on hand to answer any of your doggy issues and aim to delight you with a demonstration of happy dogs dancing, synchronized obedience and heelwork-to-music. Dima is a specialist dog trainer who has been featured on many TV programs, including ‘The Underdog Show’ and ‘Leader of the Pack’ (www.goodboydogschool.co.uk)
Getting extra on the day from our amazing supporters
1. Representatives of Husse will also be available to discuss your dog’s nutritional needs (www.husse.co.uk)
2. We are also being supported All Dogs Matters which cares for and rehomes dogs in need and can tell you everything you need to know if you are considering fostering or adopting another dog (www.alldogsmatter.co.uk)

We look forward to walking with you and having a fun day out!
For more info please contact:
Sandra: sandrahamilton@curecancer-ucl.org / 07956363832
or Dima: dimadogs@hotmail.com / 07957228269
* Getting to Kensington Gardens
•   The nearest tube is Lancaster Gate (Central Line)
•   The nearest park entrances are: Victoria Gate and Westbourne Gate off the Bayswater Road
•   Please note that there is limited parking in the park - If coming by car please use the Triangle Car Park, West Carriage Drive, Kensington Gardens W2 3

    



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Friday 15-March-2013

Scientists put the brakes on runaway brain tumours.

Published in: Genes & Development


Stefan H. Stricker, Andrew Feber, Par G. Engstrom, Helena Caren, Kathreena M. Kurian, Yasuhiro Takashima, Colin Watts, Michael Way, Peter Dirks, Paul Bertone, Austin Smith, Stephan Beck, and Steven M. Pollard

Widespread resetting of DNA methylation in glioblastoma-initiating cells suppresses malignant cellular behaviour in a lineage-dependent manner. Genes & Development, 2013 Mar 15, 27 (6). (Online)
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nature An international effort to improve our knowledge of the behaviour of one of the most aggressive and lethal forms of brain tumour has yielded exciting new insights in work funded by The Brain Tumour Charity and Cancer Research UK.

Scientists today published findings in the journal “Genes & Development” of their investigations into glioblastoma. Glioblastoma (GBM) is a form of primary brain cancer that is a major contributor to brain tumours being the biggest cancer killer of children and adults under the age of 40 in the UK. Cancer is caused by mutations in genes that are permanent. However, it is also frequently accompanied by changes to the 'switches' that control which genes are turned on or off. If the wrong genes are turned on and off, this can lead to uncontrolled growth of cells – similar to having the accelerator pressed down and the brakes failing in a car.

These gene switches - termed epigenetic regulation - are potentially reversible. However, it has been difficult to test what the consequences of reversing these would be.

Scientists working collaboratively at Samantha Dickson Brain Cancer Unit, which is funded by The Brain Tumour Charity, at UCL and at other UK units in Cambridge, Bristol, London as well as overseas in Germany and Canada, have shown that the 'brakes' can be widely reactivated by using experimental stem cell reprogramming techniques.

Importantly, the reprogramming also enabled the scientists to force the cells to acquire a different identity and become cartilage - a tissue type not normally present.

When they did this they observed the brakes to be turned back on and tumour growth to slow down. The development is exciting as the scientists were effectively able to make this aggressive cancer become benign.

A particular problem with this form of brain tumour is the way the cells infiltrate from the tumour into the surrounding brain as it grows, which results in them being extremely difficult to remove completely by surgery. After reprogramming, the scientists found a spectacular suppression of the tendency of tumour cells to invade the surrounding brain. They have identified a gene called "TES" that may have a role in this.

This study is an important step in improving our knowledge of the important pathways and gene switches that should be targeted in glioblastoma and will help prioritise testing of new drugs.

Neil Dickson, Vice-Chair of Trustees of The Brain Tumour Charity said: “We are proud to have funded this research, which we hope will lead to a greater understanding of this disease and further development of potential new treatments. Research into brain tumours receives a fraction of the funding of that of higher profile cancers and it is our priority to redress the balance. This is essential as figures show that advances in treatment, achieved through the dedicated work of committed researchers over the years, have had a beneficial effect. The results published today are an excellent validation of the work of our Centre of Excellence, the Samantha Dickson Brain Cancer Unit at UCL. These exciting findings give us new drive in our aim to award funding to two more Centres of Excellence within the year in our fight to beat this devastating disease.

Dr David Scott, Director of Science Funding at Cancer Research UK, said: “Understanding brain tumours is a real challenge facing researchers and we urgently need to greater knowledge to develop new treatments which help more people diagnosed with the disease. By working together we are able to fund more research and really focus on areas that are going to make a telling difference.

    



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Monday 11-March-2013

Order from Chaos: Deciphering the basis for Genetic Diversity in Colon cancer.

Published in: Nature


Burrell RA, McClelland SE, Endesfelder D, Groth P, Weller MC, Shaikh N, Domingo E, Kanu N, Dewhurst SM, Gronroos E, Chew SK, Rowan AJ, Schenk A, Sheffer M, Howell M, Kschischo M, Behrens A, Helleday T, Bartek J, Tomlinson IP, Swanton C

Replication stress links structural and numerical cancer chromosomal instability. Nature, 2013 Feb 28;494(7438):492-6. doi: 10.1038/nature11935. (Online)
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nature Increasing evidence suggests that individual tumours are comprised of major genetic differences between cells of the same tumour resulting in chaotic genomes in individual cancers. This results in what is known as intratumour heterogeneity that describes variation between cancer cells within one tumour. Increasing evidence suggests that the more chaotic a tumour is the harder it may be to treat and the worse the clinical outcome. Therefore understanding how diversity in tumours comes about is likely to be important to define ways in which it can be detected and how it may be limited through treatment to attempt to stop tumours changing over time.

One way in which variation in the genetic make up of cancer cells occurs is through a process called Chromosomal Instability (CIN). Chromosomes contain the genetic material present in every cell. A normal human cell has 46 chromosomes. Many cancers are aneuploid, that is they have an abnormal content of chromosomes. Worse still, this abnormal content can vary from one cell to the next, a phenomenon called chromosomal instability, generating genetic variation between cells and resulting intratumour heterogeneity.

Despite the knowledge of the existence of this problem in tumours, why this occurs in tumours is largely unclear. Researchers from the UCL Cancer Institute and Cancer Research UK have been studying this problem in colorectal cancer. They started by classifying how cells make errors in the separation of chromosomes at cell division. They found that the majority of the errors resulted from chromosomes that were fragmented or structurally abnormal, suggesting that the major defect resulting in CIN was caused by defects in the manufacture of chromosomes earlier during the cell division process when DNA is replicated (S Phase). A series of experiments demonstrated that the problem results from a phenomenon called DNA replication stress. DNA replication stress is analogous to constructing a building with insufficient cement for the foundations or too few bricks for the walls, the building collapses once built. Similarly, the chromosomes fragment and lack the proper structures to be separated accurately during cell division, resulting in the random partition of chunks of DNA between cells of the same tumour, generating diversity in a cancer. The researchers then showed that by providing the cancer cells with more building blocks of DNA (nucleotides), they could rescue the problem and lower the errors in chromosome segregation at cell division, analogous to providing more cement for the foundations or bricks for the walls.

Finally, in order to define a genetic basis for this problem in tumours, Burrell et al showed that in colorectal cancer, one chromosome is commonly very abnormal in this disease, lacking half a chromosome arm. Interestingly this chromosome arm is specifically lost in CIN colorectal cancers, suggesting that genes within that chromosome may regulate the process. Burrell et al looked one by one at the 94 genes encoded on this chromosome that are recurrently lost specifically in CIN cancers and asked whether any of them might regulate the equal division of chromosomes during cell division. They found three genes, PIGN, MEX3C and ZNF516, which when lost from normal cells by genetic disruption result in DNA replication stress and chromosome segregation errors at cell division. These results show that by using genetic techniques, order can be derived from chaotic cancer genomes to define how cancer diversity comes about. Ultimately it is hoped that one day similar approaches may be used to define how cancer's chaos can be more efficiently treated to prevent the generation of drug resistance and improve survival outcomes in this disease.

    



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Wednesday 29-January-2013

Dormant Cancer Cells explains Resistance to Therapy

Published in: Leukemia


C Lutz , P S Woll , G Hall, A Castor, H Dreau, G Cazzaniga, J Zuna, C Jensen, S A Clark , A Biondi, C Mitchell, H Ferry , A Schuh, V Buckle, S-E W Jacobsen and T Enver

Quiescent leukaemic cells account for minimal residual disease in childhood lymphoblastic leukaemia. Advance online publication 29 January 2013; doi: 10.1038/leu.2012.306 (Online)
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Flan Childhood leukaemia remains a model disease to study the biology of cancer. Important questions in cancer research are how cancer cells survive for many years before giving rise to secondaries (metastases), and why chemotherapy has to be given over many months to kill all tumour cells? The Laboratory of Prof Tariq Enver now shows that cancer cells that become dormant (quiescent) can result in residual disease after chemotherapy treatment. Dormancy could explain late relapses, as well as treatment resistance for a variety of cancer types.

    



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Tuesday 18-December-2012

Collaboration Cellectis (genome engineering) with UCL Cancer Institute to fight leukaemia


Cellectis (Paris, France), a genome engineering specialist company, announces the signing of a broad collaboration agreement with researchers at the UCL Cancer Institute on the development of a therapy program to fight leukaemia.


This agreement builds on Cellectis’ therapeutic strategy to treat patients with B-cell leukemias. This therapy uses Cellectis’ proprietary genome engineering technologies to manufacture T-cells that specifically target and destroy cancer cells. These non-patient derived (allogeneic) T-cells are engineered with Cellectis’ nucleases in order to eliminate the potential for the T-cells to attack the recipient's normal tissues, and to make them resistant to widely used anti-cancer treatments.

The use of Cellectis’ engineered allogeneic T-cells will overcome limitations of patient-derived adoptive immunotherapies by allowing the treatment of a large number of cancer patients with a standardised “off the shelf” therapy product.

Through this agreement, Dr. Martin Pule, Dr. Karl Peggs, and other members of the UCL Research Department of Haematology, who are global leaders in adoptive immunotherapy, will work with Cellectis towards in vivo proof of concept and clinical translation of this strategy.

  View Cellectis Press-release
  



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Wednesday 17-October-2012

Common Genetic Variant Strongly Linked to Rare Bone Cancer

Published in: Nature Genetics


Nischalan Pillay, Vincent Plagno, Patrick S Tarpey, Samira B Lobo, Nadège Presneau, Karoly Szuhai, Dina Halai, Fitim Berisha, Stephen R Cannon, Simon Mead, Dalia Kasperaviciute, Jutta Palmen, Philippa J Talmud, Lars-Gunnar Kindblom, M Fernanda Amary, Roberto Tirabosco & Adrienne M Flanagan

A common single-nucleotide variant in T is strongly associated with chordoma Nat Genet. 2012 Oct 14. doi: 10.1038/ng.2419. (Online)
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Flan A genetic variation possessed by 40% of the population is associated with a five-fold increase in risk for developing chordoma, a cancer that strikes the bones of the skull and spine.

A team of scientists at University College London (UCL), Royal National Orthopaedic Hospital (RNOH), and the Wellcome Trust Sanger Institute in the UK found that over 95% of European chordoma patients have a single letter variation in the DNA sequence of a gene called brachyury. The team found that people with the altered version of the brachyury gene are over five times more likely to develop chordoma than the general population. The increase in risk of developing chordoma caused by this alteration in brachyury comes close to the increase in risk of developing breast cancer caused by mutations in the BRCA1 and BRCA2 genes.

    

The results, published today in the journal Nature Genetics, are the latest outcome of the Chordoma Genome Project, a collaborative effort funded by the Chordoma Foundation, which aims to catalogue all of the genetic changes that drive chordoma in hopes of identifying new targets for treatment. The Rosetrees Trust and Skeletal Cancer Action Trust (Scat), UK provided additional support for this research.

Chordoma is a rare and devastating form of cancer. It frequently returns after surgery, and is resistant to radiation and conventional chemotherapy. Most patients ultimately succumb to their disease after an average of seven years. No drugs are approved to treat chordoma, and, until recently, little was even known about the biology that drives chordoma.

“Our finding that this variation is associated with a five-fold increase in the risk of developing chordoma is remarkable in cancer genetics, as almost all other genetic variants associated with cancer cause only a modest (less than two-fold) increase in risk,” explains Dr. Adrienne Flanagan of UCL and RNOH, who led the study. “This study makes a strong case that this particular variation in the brachyury gene contributes significantly to the development of chordoma in nearly all patients. It is a major step forward in our understanding of how chordoma develops, and can open the door to the development of an effective, targeted treatment.”

Brachyury is a gene of emerging significance for cancer. In addition to chordoma, it has recently been implicated in other types of cancer, including colon cancer and lung cancer. It is highly expressed in nearly all chordomas as well as a number of other cancers, but not in normal tissues. Most notably, in 2009, scientists found that inheriting an extra copy of brachyury is responsible for causing familial chordoma. Individuals with familial chordoma receive three copies of this gene rather than the two copies normally inherited, one each from mother and father. This latest finding confirms that the brachyury gene also plays a central role in the more typical sporadic (non-familial) version of the cancer.

Recently, Dr. Flanagan and colleagues demonstrated that genetically ‘silencing’ brachyury stops the growth of chordoma cells in laboratory experiments. In a paper published in the current issue of the Journal of Pathology, they also showed that brachyury acts as a master regulator of a network of molecules that contribute to uncontrolled growth of chordoma cells.

“Understanding the genetic underpinning of chordoma is a key step in the Chordoma Foundation’s research roadmap,” said Josh Sommer, Executive Director of the Chordoma Foundation. “This discovery is an encouraging outcome of the Foundation’s investment in the Chordoma Genome Project over the past three years. Finding a single genetic change that is so frequent in chordoma creates exciting opportunities to pursue therapies that target the defining nature of the disease.”

Upcoming research will focus on understanding why the alteration in brachyury is so critical for chordoma development, and what other factors are at play. Answering these questions may enable scientists to develop an effective treatment that reverses or blocks the effect of the alteration. Efforts are underway in the Flanagan lab to develop a means of inhibiting brachyury and the pathway of molecules it controls in cancer.

The research team is currently poised to launch the next phase of the Chordoma Genome Project, which will attempt to determine what actually triggers the development of chordoma once the brachyury variation creates the predisposition. This project is set to start as soon as the Chordoma Foundation can raise $47,000 to fund this work.

About the Chordoma Foundation
The Chordoma Foundation was established in 2007 to accelerate the development of effective treatments and ultimately a cure for chordoma, a devastating bone cancer of the skull and spine. The Foundation strategically funds research, distributes biological materials needed for research, and facilitates communication and collaboration among scientists and physicians.

Since 2009, the Foundation has funded the Chordoma Genome Project, a collaboration between researchers at the Wellcome Sanger Institute, University College London, and the Royal National Orthopaedic Hospital, which aims to uncover systematically all of the genetic changes that drive chordoma and thereby identify targets for treatment. Upcoming Chordoma Foundation research efforts will attempt to determine how the recently discovered genetic predisposition contributes to the development of chordoma, and exploit this discovery to develop targeted therapies for chordoma. To learn more about the Chordoma Foundation and what you can do to help, please visit www.chordoma.org.




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Tuesday 16-October-2012

Skin rash predicts survival benefit from latest lung cancer drug

Published in: Lancet Oncology


Siow Ming Lee, Iftekhar Khan, Sunil Upadhyay,Conrad Lewanski, Stephen Falk, Geraldine Skailes, Ernie Marshall, Penella J Woll, Matthew Hatton, Rohit Lal, Richard Jones, Elizabeth Toy, David Chao, Gary Middleton, Sue Bulley, Yenting Ngai, Robin Rudd, Allan Hackshaw, Chris Boshoff.

First-line erlotinib in patients with advanced non-small-cell lung cancer unsuitable for chemotherapy (TOPICAL): a double-blind, placebo-controlled, phase 3 trial.
Lancet Oncology (2012), DOI: 10.1016/S1470-2045(12)70412-6 (Online).


Lee ELDERLY patients with advanced non small cell lung cancer (NSCLC) who developed a rash within 28 days of receiving the targeted drug erlotinib (Tarceva) survived on average 6.2 months, compared to 2.9 months among those who didn’t develop a rash, results from a major phase III Cancer Research UK-funded trial show today (Tuesday).*

And for patients who, in addition to developing the painless rash, also carried mutations in the epidermal growth factor receptors (EGFR) on the surface of their cancer cells, the survival time was even greater at 10.4 months.**

    

Around eight in 10 cases of this form of lung cancer occur in people aged 60 and over, and the average age of patients in the UK is 72 years. Many of these elderly patients are diagnosed at a late stage and already have other illnesses, meaning they are often too frail to be treated with conventional chemotherapy. This means that palliative care is usually the only option available to them.

These trial results show that giving erlotinib to these patients can significantly improve survival, if they develop a rash due to the drug.

The findings are published in the journal Lancet Oncology today.

Chief investigator Professor Siow Ming Lee, clinical researcher for Cancer Research UK at the UCL Cancer Institute and consultant at the UCL Hospital Trust, said: “The vast majority of NSCLC patients are elderly and diagnosed at a late stage, often leaving them too frail to cope with the rigours of chemotherapy. Until now, the only option for these patients has been palliative care. But these trial results offer potential hope, with six in every 10 patients who received erlotinib developing a rash that signalled whether or not they were benefitting from this drug treatment. This is extremely encouraging and represents a significant step forward for this group of patients, who often only have a short time left to live.

“Interestingly, we found that women who developed a rash after taking erlotinib tended to survive longer than men. And smokers were less likely to develop a rash than non-smokers or former-smokers when treated with erlotinib. Further studies to understand the link between skin rash and erlotinib response are urgently needed to find ways of exploiting this relationship for maximum benefit.”

Six-hundred and seventy patients took part in the study from 78 hospitals around the UK, conducted by Cancer Research UK and the UCL Cancer Trials Centre. They were randomly assigned to receive tablets containing either erlotinib or a placebo. All patients had advanced stage NSCLC, the majority were aged over 75 and almost all had two or more other medical conditions and were not suitable for chemotherapy treatments.


¯¯¯¯¯¯¯¯¯¯¯¯¯
* Siow Ming Lee et al., First-line erlotinib in patients with advanced non-small-cell lung cancer unsuitable for chemotherapy (TOPICAL): a double blind, placebo-controlled, phase 3 trial , Lancet Oncology (2012), DOI: 10.1016/S1470-2045(12)70412-6

** Skin changes occur in about 3 in 4 people (75%) who take erlotinib – patients may have a rash, blistering, or red, dry, skin, which usually starts within 10 days of starting the drug. If it is severe the dose may be reduced or doctors may stop treatment.




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4-06-2012

Blood test provides ‘snapshot’ of tumour drug response

Presented at: 2012 ASCO Annual Meeting


Mohid Shakil Khan, Theodora Tsigani, Jorge Garcia-Hernandez, John Anthony Hartley, Martyn E Caplin, Tim Meyer. Circulating tumor cells as prognostic and predictive markers in neuroendocrine tumors. J Clin Oncol 30, 2012 (suppl; abstr 4123) (Online).


COUNTING the number of tumours cells in blood samples taken before and after treatment for advanced neuroendocrine tumours could provide a ‘snapshot’ of how well patients are responding within weeks of starting treatment, according to results from a study being presented at the American Society for Clinical Oncology cancer conference today (Monday).

    Meyer

The study, coordinated by researchers from the Cancer Research UK and NIHR Experimental Cancer Medicine Centre (ECMC) at UCL, is the largest of its kind and the first to demonstrate how monitoring cancer cells circulating in the blood can be used to predict treatment success for this rare cancer-type, which most commonly affects gastrointestinal tract and pancreas.

The researchers analysed blood samples from 118 patients with advanced neuroendocrine cancers before and after treatment and compared the number of tumour cells present in each sample. Patients in whom circulating tumour cells (CTCs) were detectable in the blood at the start of treatment were eight times more likely to die from their disease compared to those with undetectable CTCs. Following treatment, the prognosis was significantly better in those who had a more than two thirds fall in the number of CTCs and worst in those that had a rise of more than a third. Importantly, these changes occurred within 2-5 weeks after starting a new treatment.

Study leader Dr Tim Meyer, who directs UCL ECMC, said: “By using state-of-the-art technology to count individual tumour cells circulating in the blood stream, we’ve been able to show how a simple blood test could provide important information about prognosis and response to treatment in these patients. Doctors normally rely on CT or MRI scans to tell them if a treatment is working, but cutting-edge CTC testing can provide an overall snapshot of the tumour’s development, without the need to wait for changes in its size to become visible on scans.

“Although these findings are preliminary, CTC testing is already showing promise in advanced breast, prostate and colorectal cancers and, on the basis of these results, is being incorporated into several trials involving patients with neuroendocrine cancers. This will help uncover ways of determining the impact of treatment on a cellular level, helping tailor treatment to individual patients.”

Dr Joanna Reynolds, Cancer Research UK’s director of centres, said: “This is a great example of how the Experimental Cancer Medicine’s Network is supporting cutting-edge research into rarer cancer types. Advanced cancers often consist of lots of smaller tumours around the body, many of which will be too tiny to be picked up by traditional imaging techniques, making it difficult to judge how well a drug is working. This study highlights a potential way to monitor response in real time across all cancer sites, so doctors know sooner if a treatment isn’t working. Although at an early stage, this is an exciting area of research and we look forward to seeing how it progresses.”




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3-05-2012

Trial transforms thyroid cancer treatment into safer and shorter session

Published in: The New England and Journal of Medicine.


Ujjal Mallick, F.R.C.R., Clive Harmer, F.R.C.P., Beng Yap, F.R.C.P., Jonathan Wadsley, F.R.C.R., Susan Clarke, F.R.C.P., Laura Moss, F.R.C.P., Alice Nicol, Ph.D., Penelope M. Clark, F.R.C.Path., Kate Farnell, R.C.N., Ralph McCready, D.Sc., James Smellie, M.D., Jayne A. Franklyn, F.Med.Sci., Rhys John, F.R.C.Path., Christopher M. Nutting, M.D., Kate Newbold, F.R.C.R., Catherine Lemon, F.R.C.R., Georgina Gerrard, F.R.C.R., Abdel Abdel-Hamid, F.R.C.R., John Hardman, F.R.C.R., Elena Macias, M.D., Tom Roques, F.R.C.R., Stephen Whitaker, M.D., Rengarajan Vijayan, F.R.C.R., Pablo Alvarez, M.Sc., Sandy Beare, Ph.D., Sharon Forsyth, B.Sc., Latha Kadalayil, Ph.D., and Allan Hackshaw, M.Sc.

A new gold standard for thyroid cancer treatment has been set, reducing radiation doses to just one third of the current level, according to research from the CRUK-UCL Cancer Trials Centre. The results are published in the New England Journal of Medicine.

Patients currently have surgery to remove the entire thyroid gland. A few weeks later they take a capsule containing radioactive iodine which destroys any remaining healthy thyroid gland tissue and any potential cancer cells. Improvements in surgery mean more of the thyroid gland is removed during the operation, leaving fewer remaining cells to be ‘mopped up’ - so lower radiation doses are adequate and equally effective.

The HiLo trial of 438 patients at hospitals across the UK, led by researchers at UCL’s Cancer Institute, showed that giving selected patients a much lower dose of radioactive iodine in a single oral capsule delivers similar treatment success to the current higher dose - destroying all thyroid gland cells remaining after surgery, with fewer side effects.

The higher doses of radioactive iodine previously thought necessary meant that patients had to stay in a hospital isolation unit for at least two days while the radiation left their bodies, without physical contact from family and friends. These high doses could have several side effects – the more serious of which occur later in life, such as a permanent dry mouth, and a small chance that a new cancer will develop.

However, patients taking the lower dose capsule can be treated as an outpatient. The process is easier, quicker (hours, rather than days), and patients experience fewer side effects.

The thyroid gland makes and releases hormones. After it is removed patients require thyroid hormone tablets for the rest of their lives. Radioactive iodine works best when patients stop taking thyroid hormone tablets two to four weeks beforehand, but this leads to side effects such as lethargy, fatigue and weight gain, reducing patients’ quality of life and their ability to function at home and at work.

A secondary finding of the HiLo study is that patients can avoid these symptoms if they continue to take thyroid hormone tablets and are also given an injection of Thyroid Stimulating Hormone (Thyrogen) just before they take the low dose radioactive iodine.

"HiLo is a seminal trial that will affect how most thyroid cancer patients will be treated,” says Professor Allan Hackshaw, a senior author of the paper and leader of the HiLo trial at the CRUK-UCL Cancer Trials Centre. “Health professionals have waited several decades for reliable research to show that a lower dose of radioactive iodine can be used instead of the standard high dose. Future patients will thus have a shorter and safer treatment".

Lead study author, Dr Ujjal Mallick, at the Freeman Hospital in Newcastle, says: “We’re delighted that this study of thyroid cancer will change international approaches to treat the disease more safely, by reducing the chance of another cancer developing later in life and other side effects.

“Patients will have a much better quality of life. They’ll be treated much more quickly, which will keep the disruption to their lives to a minimum, as well as saving the NHS money.”

Kate Law, director of clinical research at Cancer Research UK, says: “This pivotal study – which is the first for thyroid cancer in the UK – heralds a vastly improved treatment for the disease.

“Being treated as an outpatient means that patients should be able to be in their home surroundings on the same day as the treatment. The lower dose of radiation and thyrogen will help them carry on with their lives as usual at work or at home without requiring several days to recover.

“More than 2,100 people are diagnosed with thyroid cancer in the UK every year – and it has the fastest rising incidence rate of the most common cancers in the UK. We’re continuously striving to improve treatments and reduce side effects for this type of cancer.”




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14-04-2012

Olaparib Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer

Published in: The New England and Journal of Medicine.


Jonathan Ledermann, M.D., Philipp Harter, M.D., Charlie Gourley, M.B., Ph.D., Michael Friedlander, M.B., Ph.D., Ignace Vergote, M.D., Ph.D., Gordon Rustin, M.D., Clare Scott, M.B., Ph.D., Werner Meier, M.D., Ph.D., Ronnie Shapira-Frommer, M.D., Tamar Safra, M.D., Daniela Matei, M.D., Euan Macpherson, M.Sc., Claire Watkins, M.A., M.Sc., James Carmichael, M.D., and Ursula Matulonis, M.D.

Olaparib is a new anti-cancer agent that targets a specific DNA repair pathway by blocking a PARP (Poly ADP ribose polymerase) enzyme. Treatment with olaparib produces shrinkage in more than a third of patients with ovarian cancer who have a defective BRCA gene. Patients with a mutation in a BRCA gene have a deficiency of DNA repair by homologous recombination, the pathway by which normal cells repair DNA damage in the presence of a PARP inhibitor. Deficiency of homologous recombination repair and inhibition of PARP in these tumours results in cell death by ‘synthetic lethality’. Inherited BRCA mutations are seen in about 15-20 % of patients with ovarian cancer but homologous recombination deficiency may be present in up to 50 % of high-grade serous ovarian cancers due to non inherited defects in BRCA genes and other non-BRCA related mechanisms.

In the New England Journal, March 27th 2012 Prof Jonathan Ledermann at UCL Cancer Institute and international co-investigators published the results of a trial he led to evaluate the activity of olaparib, as maintenance therapy in patients with recurrent high grade serous ovarian cancer. BRCA gene mutations were known to be present in some patients on the trial. The trial tested whether olaparib given after the completion of chemotherapy for recurrent disease delayed further progression or recurrence of ovarian cancer.

The trial was conducted by AstraZeneca, the manufacturer of olaparib and run in 82 sites in 16 countries. 265 patients were randomly assigned to olaparib maintenance or placebo following the completion of chemotherapy. There was a highly significant delay in tumour progression in patients taking olaparib. The median progression-free survival after the end of chemotherapy was 8.4 months compared to 4.8 months (hazard ratio 0.35; 95% CI 0.25–0.49; P<0.00001). Sixty-eight (50%) and 21 (16%) patients, respectively, remained on olaparib or placebo treatment at data cut-off.

However, an interim analysis of survival on immature data has thus far failed to show a survival benefit. It is possible that there are subgroups of patients who respond better and for longer, and this is being investigated further. At the time of publication of the trial 21 % of women remain progression-free on olaparib more than 21 months after study closure, compared to 3 % who are on placebo. Olaparib is a highly active drug and further investigation of the data is required to understand how to bring this highly active drug into more regular clinical use.




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12-04-2012

How to get loaded with new histones

New study from the UCL Cancer Institute discovers a novel mechanism underlying histone loading in the central nervous system


The main focus of Professor Paolo Salomoni’s laboratory is on mechanisms underlying central nervous system (CNS) pathophysiology, in particular brain cancer development. They have recently discovered a novel mechanism regulating epigenetic changes in the CNS. This work is published in the April issue of Neuron.
Modifications of chromatin are believed to contribute to cancer development. In particular, the process of transformation is known to dramatically alter the chromatin landscape. However, the molecular mechanisms underlying these modifications and the regulatory pathways involved are not fully understood. Their work on a chromatin-associated factor called DAXX, which interacts with the tumour suppressor PML and has been recently discovered to act as chaperone for the histone variant H3.3. Loading of this histone variant has been implicated in chromatin remodeling at transcribed loci, heterochromatin and telomeres. Remarkably, somatic mutations in the gene encoding H3.3 have been recently found in paediatric cases of the brain neoplasm glioblastoma multiforme along with components of its chaperone complex, DAXX and ATRX, which are also mutated in neuroendocrine tumours of the pancreas. H3.3 is the first histone found mutated in human cancer. Overall, these studies propose a whole new concept whereby alterations of histone variant loading may contribute to disease pathogenesis in the CNS. However, we know very little about the mechanisms underlying deposition of H3.3 in the CNS and its potential involvement in transcriptional regulation.
This study shows that DAXX is associated with regulatory regions of selected genes in the CNS, where it promotes H3.3 loading upon neuronal activation. DAXX loss not only affects H3.3 deposition but also impairs transcriptional induction of these genes. Moreover, they have demonstrated that calcineurin-mediated dephosphorylation of DAXX is a key molecular switch controlling its function. Overall, these findings implicate the H3.3 chaperone DAXX in the regulation of calcium-triggered events, thus revealing a novel mechanism underlying epigenetic modifications in the CNS. Alterations of DAXX-mediated control of histone loading could be involved in brain cancer development as well as pathogenesis of other CNS conditions. Exciting times lie ahead for research in this area.

Michod D, Bartesaghi S, Khelifi A, Bellodi C, Berliocchi L, Nicotera P, and Salomoni P. Calcium-dependent dephosphorylation of the histone chaperone DAXX regulates H3.3 loading and transcription upon neuronal activation. Neuron, Volume 74, Issue 1, 122-135, 12 April 2012 (Online) .

    Salomoni
 


Legend: The image shows two nucleosomes depicted as neurons with DNA wrapped around them. Different color codes indicate i) the presence of either the canonical histone H3 (yellow) or its variant H3.3 (pink) and ii) the associated changes in epigenetic information and transcriptome.




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03-04-2012

‘Momentous occasion’ as University College Hospital Macmillan Cancer Centre opens its doors


macmillan

The University College Hospital Macmillan Cancer Centre will open its doors to patients for the first time this week – offering the most advanced service of its kind in the UK.

Patients have been involved in the design of the centre and its services every step of the way, from the light and airy entrance hall and uplifting colour scheme to the development of a web-hosted ‘patient portal’ which gives them more control over their care.

The centre will redefine the way patients are treated, focusing on all aspects of their outpatient care. The close links to the UCL Cancer Institute, which is directly across the road, will give them the opportunity to take part in leading-edge clinical trials.

The £100 million development has wellbeing, rehabilitation and cancer survivorship at the heart of its philosophy. This will be supported by the very best diagnostic and treatment techniques to improve survival rates, including the UK’s first PET MR scanner, delivering the most accurate information from deep inside the body during a single scanning session.

The centre has been developed in partnership with Macmillan Cancer Support, who bring 100 years’ experience of developing innovative, ground-breaking services which put the needs of patients and families at the heart of cancer care. The centre is Macmillan’s largest-ever investment of £10 million. It will also see UCLH continuing its long-standing partnerships with Teenage Cancer Trust and HCA International.

macmillan Dr Kirit Ardeshna, UCLH clinical lead for the new cancer centre and a consultant haematologist, said: “Our new centre will truly focus on every detail of the patient journey. With earlier diagnosis and advances in drug treatments, many patients with cancers are now cured. For other patients cancer is more like a chronic disease characterised by long periods when the disease is stable, punctuated with periods of intense activity.
“For these patients it is very much about living with cancer and living to your full potential – not letting cancer treatments interfere too much with your quality of life. Our new cancer centre will reflect this shift and hopefully make the patients’ journey as pleasant as possible.”

Patients have been consulted on the design of the centre through representatives on UCLH working groups.

Daphne Earl has lived with the experience of cancer for 40 years. First her mother, then father and – most devastatingly – her beloved six-year-old son Marc died from the disease. Thirty years later, Daphne too was diagnosed with non-Hodgkin’s lymphoma.

Daphne welcomed the opportunity to be able to influence the design and philosophy of the new centre: “It’s now increasingly accepted that a patient should be viewed as a whole person with prior experiences, not as a ‘one size fits all’ statistic who happens to have a particular type of cancer.”

Sir Robert Naylor, UCLH chief executive, said: “The opening of the cancer centre is a significant development in our ambition to become a leader in the provision of cancer care. Quite simply, the centre is the realisation of a long-term dream.

“Ten years ago we visited the Memorial Sloan-Kettering Cancer Center in the USA, and were impressed by the way they treated cancer – out of hospital wherever possible and a service that was designed around the needs of the patient, not the other way around. We were left with the question, why can’t we do that here? Now, the cancer centre gives us the opportunity to do this and so much more.”

Macmillan will provide a Support and Information Service, in which an experienced team of staff and trained volunteers will offer individual support, information and practical advice to patients, family members, friends and carers. The Macmillan team will support 100 patients a day with a range of issues, from financial problems to help getting back to work. Complementary therapies, such as massage and aromatherapy will be available to patients and carers as well as support for the physical and emotional effects of cancer at every stage.

macmillan Ciarán Devane, chief executive of Macmillan Cancer Support, said: “This is a truly momentous occasion for the two million people living with cancer right now. Ten years ago we had a vision to fundamentally change the way cancer care is delivered by ensuring patients are always at the centre. It’s incredible to see this finally realised in this centre which will provide world-leading, sustainable cancer care by radically redesigning the way cancer patients are treated.

“Patients have helped design the centre to ensure that they will be put in control of their own care. Not only will patients receive the very best treatment and benefit from the latest research, but they can expect an experience to match. This partnership with UCLH will be a blueprint for how we can work with trusts in the future to deliver innovative services that redefine standards for cancer care and improve the lives of cancer patients for years to come.”

The total charitable effort (overseen by UCLH Charitable Foundation) will raise £30 million, with the single largest donation coming from Macmillan. The Teenage Cancer Trust has contributed £2.6 million to develop a state-of-the-art day treatment centre for teenage and young adult patients. It complements the existing Teenage Cancer Trust inpatient unit at University College Hospital that has been supporting young people with cancer since 2005.

Known as the Teenage Cancer Trust Hub, the unit will provide outpatient care, treatment and consultation for young people with cancer aged from 13 to 24. Featuring the very best in interior design and technology, The Hub consists of treatment pods, consulting rooms, private treatment rooms and a recreation area. Designed and based on the ideas of young people, The Hub also includes a gym, DJ booth, computer gaming space, education zone, family area and cafe.

macmillan HCA International is leasing the fifth floor and will open a dedicated private cancer and haematology centre early in May. This is building on a long-standing partnership between UCLH and HCA which began at University College Hospital in 2006 and allows a share of proceeds to be invested back into the NHS.

The centre, in Huntley Street, WC1E 6AJ, was designed by Hopkins Architects, the award-winning firm responsible for the iconic Velodrome created for the 2012 London Olympic and Paralympic Games. It was built by leading construction company Skanska, recently named the greenest company in the UK across all industries in The Sunday Times Best Green Companies Awards.

The centre will achieve environmental as well as clinical excellence. By making efficient use of natural light, and using a very innovative glazing system the building will meet the newly announced NHS environmental targets eight years early. Carbon emissions will be cut by a third. The development includes both a green roof and photovoltaic panels for on-site energy generation.

 
macmillanView the opening on BBC i-Player



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08-03-2012

DNA analysis shows huge genetic diversity in tumours



genetic diversity in tumours

Taking a sample from just one part of a tumour may not give a full picture of its "genetic landscape" says Prof. Charles Swanton (UCL Cancer Institute).

Published in the New England Journal of Medicine


From The New England Journal of Medicine

Professor Charles Swanton, based at the UCL Cancer Institute and Cancer Research UK’s London Research Institute has shown that taking a sample from just one part of a tumour may not give a full picture of its ‘genetic landscape’. He comments “We’ve known for some time that tumours are a ‘patchwork’ of faults, but this is the first time we’ve been able to use cutting-edge genome sequencing technology to map out the genetic landscape of a tumour in such exquisite detail.”

The study is published in the New England Journal of Medicine, 8th March 2012, and shows the first ever genome-wide analysis of the genetic variation between different regions of the same tumour using kidney cancer samples. They found that the majority, around two thirds of gene faults, were not found in other biopsies from the same tumour. They identified 118 different mutations – 40 of which were ‘ubiquitous mutations’ found in all biopsies, 53 ‘shared mutations’ that were present in most but not all biopsies and 25 ‘private mutations’ that were only detected in a single biopsy.

By analysing the location of shared mutations in relation to the whole tumour, the researchers at Cancer Research UK were able to trace the origins of particular subtypes of cancer cells back to key driver mutations. This allowed them to create a ‘map’ of how the pattern of faults within the tumour might have evolved over time.

For realated links see:




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20-02-2012

Generous donation from Cure Cancer @ UCL


Cure Cancer

Professor Tariq Enver and Dr Rajeev Gupta where delighted by receiving a generous equipment donation from Cure Cancer @ UCL. 'Cure Cancer @ UCL' is a charity that has been set up by Mrs Sandra Hamilton (who suffers with lymphoma) and her family. Its aim is to support basic research on the biology of lymphoma in the stem cell laboratory at the UCL Cancer Institute. At the end of 2011, the charity raised over £70000 and purchased several items of equipment for the laboratory like centrifuges and a Real Time PCR machine. On the 20th Feb 2012, Professor Enver and Dr Gupta hosted an event at the UCL Cancer Center for the Cure Cancer committee and senior fundraisers during which they gave an overview of their research strategy and conducted lab tours showint the new equipment in action.




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3-01-2012

Elspeth Payne wins Wellcome-Beit Prize


Elspeth Payne wins Wellcome-Beit Prize. The Wellcome-Beit Prize Fellowships are intended to provide additional recognition for four outstanding biomedical researchers who have been awarded other Wellcome Trust fellowship funding. The awards were inaugurated in 2009 and replaced the Beit Memorial Fellowships for Medical Research.




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13-12-2011

Debbie Fund has raised over £1,000,000


Debbie fund

Debbie Fund is delighted to announce that a generous donation from city brokers ICAP following their 2011 Charity Day has taken the sum raised by the Debbie Fund to over £1,000,000 in only 22 months.

Lewis Hamilton, Nathaniel Parker and Imogen Stubbs made guest appearances at the ICAP Charity Day for Debbie Fund. Sarah Phillips, Debbie’s younger daughter, together with Richard Sutton-Mattocks, Chairman of the UCL Cancer Institute Research Trust, and Helen Jameson represented Debbie Fund. The ICAP Charity Day raised a staggering $20 million worldwide for their supported charities.

In September Debbie Fund held a glittering Ball at The Hurlingham Club hosted by Nathaniel Parker. Douglas Hodge performed “I am” from his Olivier and Tony award-winning performance in La Cage Aux Folles, Laila Rouass drew the raffle and Faryl Smith and Sarah Phillips sang a duet. Other well known faces, including Formula 1 supremo Bernie Ecclestone, were at the event.

Nathaniel Parker said:

I am thrilled that Debbie Fund has crossed the landmark figure of £1,000,000. The fact that such a young charity doing such important work has got there so quickly is quite remarkable.

Professor Chris Boshoff, Director of the UCL Cancer Institute, said:

The Debbie Fund has reached the £1 million milestone. This incredible effort will provide funding essential to improve our understanding of cervical cancer and to develop effective new therapies for this devastating disease.


Notes to Editors

  • The Debbie Phillips Cervical Cancer Research Fund (“Debbie Fund”) is part of the UCL Cancer Institute Research Trust (RCN 1135220). It was set up following the death of Debbie Phillips from cervical cancer on 11th February 2010.
  • For details of Debbie Fund and its work see: the Debbie fund website
  • For details of the ICAP Charity Day see: the ICAP homepage.


For further information please contact:
Richard Sutton-Mattocks
07954 574005 or rgsm26@aol.co.uk






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10-12-2011

UCL Cancer Institute scientists publish landmark gene therapy trial


Clinical trial

Scientists, led by Dr Amit Nathwani, published in the New England Journal of Medicine on Saturday the remarkably encouraging results of patients treated with Haemophilia B (factor IX defiency) with gene therapy.

Merry Christmas for Patients with Hemophilia B
By Katherine P. Ponder, M.D.

Editorial from The New England Journal of Medicine

Hemophilia B (also known as Christmas disease) is due to deficiency of coagulation factor IX (FIX). In this issue of the Journal, Nathwani et al. report the first unequivocal evidence of successful gene therapy for hemophilia B — a major advance in this field. This success for hemophilia may translate into gene therapy for other blood protein deficiencies.

Hemophilia is due to deficiency in a coagulation factor and results in a bleeding disorder that often involves joints and muscles. The most common types are hemophilia A and B, which are due to deficiencies of factor VIII and FIX, respectively, and show X-linked inheritance. The first written account of hemophilia was in the 2nd century in the Babylonian Talmud, when Rabbi Judah decreed, “If she circumcised her first child and he died, and a second one also died, she must not circumcise her third child.”

The first reported case of hemophilia due to FIX deficiency was in 1952 and was called “Christmas disease” after the patient, a 10-year-old boy named Stephen Christmas. Queen Victoria of the United Kingdom (1819–1901) was the most famous carrier of the hemophilia B gene. Although the protein and the gene were not known during her lifetime or the lifetimes of her affected male progeny (members of the royal families of the United Kingdom, Spain, Germany, and Russia), recent analysis of polymerase-chain-reaction assays of bones exhumed from the graves of Czar Nicholas II and his family showed that the FIX gene was mutated in his son Alexei Romanov, who had hemophilia. At least nine sons, grandsons, or great-grandsons of Queen Victoria were affected with hemophilia B, and the average age at death was 24 years.

FIX concentrates were first used in the late 1960s to treat patients with hemophilia B, and their routine use for bleeding episodes increased the median lifespan to 63 years. Although enthusiasm for protein therapy was temporarily dampened by the HIV epidemic in the early 1980s, improved methods for producing FIX have increased its safety. Recently, implementation of prophylactic rather than on-demand treatment has reduced the risk of crippling joint disease.

With the success of protein therapy, why would gene therapy be needed? In the United States and other developed countries, annual costs for a single adult patient of clotting factors for hemophilia are approximately $150,000 for on-demand therapy and $300,000 for prophylaxis, which could incur a lifetime cost of over $20 million. In developing countries, prophylactic and frequent on-demand therapy is not affordable, and patients still have chronic joint disease and die young. Nathwani et al. report the truly remarkable finding that a single intravenous injection of an adenovirus-associated virus (AAV) vector that expresses FIX can successfully treat patients with hemophilia B for more than a year.

AAV is a small (4.8 kb), nonpathogenic, single-stranded DNA virus from the parvovirus family. The vector was generated by replacing the coding sequence for the cap and rep genes of the virus with a liver-specific promoter and the FIX coding sequence. The vector was packaged in cells that express cap and rep from a different piece of DNA that does not enter viral particles, thus generating a replication-incompetent vector that cannot propagate after gene transfer. Preclinical studies had shown that AAV vectors could be expressed from liver in large animals for at least 10 years. In this study, patients were treated with an AAV vector that used the capsid protein from serotype 8 (AAV8). Two patients received 2×1011 viral particles per kilogram of body weight and achieved about 1% of normal FIX activity, two patients received a threefold higher dose and achieved about 2.5% of normal activity, and two patients received a 10-fold higher dose and achieved about 7% of normal activity. Expression has been seen for over 6 months in all patients, and prophylactic use of factor concentrate has either been eliminated or reduced. Since the vector is estimated to cost $30,000 per patient, dramatic cost savings have already been achieved.

Should the practicing hematologist rush to order this gene therapy vector if it is approved by the Food and Drug Administration? The answer is probably yes, but the risks of this procedure are not yet totally clear. In one patient in this AAV8 trial, alanine aminotransferase levels were found to be about five times the upper limit of normal at 2 months after gene therapy, and there was in vitro evidence of cytotoxic T lymphocytes (CTLs) that reacted with epitopes of the AAV8 capsid protein. Prednisolone therapy resulted in normalization of the liver enzyme level within a month, and FIX expression at 6 months was 3% of normal, which was 30% of the peak FIX activity seen shortly after gene therapy. A somewhat similar result was seen in a previous trial of hemophilia B gene therapy with an AAV2 vector, in which an increase in liver enzyme levels was associated with the generation of CTLs specific for the AAV2 capsid protein. However, this patient completely lost FIX expression, leading the investigators to conclude that the CTL response destroyed all transduced liver cells. The finding that the CTL response eliminated transduced cells and gene expression in the AAV2 but not in the AAV8 trial may be related to the glucocorticoid therapy used in the latter study. Alternatively, the more rapid uncoating of AAV8 than of AAV2 capsid proteins from viral particles may allow the AAV8 capsid proteins to be degraded by most transduced cells before the immune system can find and destroy them. These results raise the concern that patients with a more recent immunologic memory of the AAV8 capsid may develop a fulminant hepatitis.

In sum, this gene therapy trial with an AAV8 vector for hemophilia B is truly a landmark study, since it is the first to achieve long-term expression of a blood protein at therapeutically relevant levels. If further studies determine that this approach is safe, it may replace the cumbersome and expensive protein therapy currently used for patients with hemophilia B. This technology may soon translate into applications for other disorders, such as lysosomal storage diseases, alpha1-antitrypsin deficiency, and hyperlipidemias.

Disclosure forms provided by the author are available with the full text of this article at NEJM.org.

This article (10.1056/NEJMe1111138) was published on December 10, 2011, at NEJM.org.






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11-11-2011

The 11/11/11 Competition


111111competition

We would like to thank everyone who submitted entries and the judges for taking time to choose the winning entries. We had over 100 images submitted and all were exceptional which made judging very difficult. The winning entries can now be seen in the POGB Cafe and once framed will be put on display in the Institute.

The Winning entries are:

1st By viewing a subject in extreme close-up it suddenly takes on a whole different perspective. As scientists our job is to examine our field of interest in great detail and learn as much as we can in the hope that our different perspective will lead to a jump forward in knowledge. Photograph taken May 2011 Location: London - Crista Illingworth

2nd Dodgems: This fairground was due to open a couple of days after the accident and consequently was never used. I recently visited Pripyat and Chernobyl and it's interesting to see how nature is reclaiming after a failure of science/technology. This was shot in early September this year - John Bingham

3rd Pelicans Kalbarri, Australia, March 2009 - John Hartley







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6-11-2011

Ollier disease and Maffucci syndrome are caused by somatic mosaic mutations of IDH1 and IDH2


M Fernanda Amary, Stephen Damato, Dina Halai, Malihe Eskandarpour, Fitim Berisha, Fiona Bonar, Stan McCarthy, Valeria R Fantin, Kimberly S Stralley, Samira Lobo, Will Aston, Claire L Green, Rosemary E Gale, Roberto Tirabosco1, Andrew Futreal, Peter Campbell, Nadège Presneau, Adrienne M Flanagan

Corresponding author: Adrienne M Flanagan (a.flanagan@ucl.ac.uk)
Letter in Nature Genetics – on line November 6th

cartilaginous_tumours Recently research performed at UCL Cancer Institute and the Royal National Orthopaedic Hospital, NHS trust with collaborators in The Wellcome Trust Sanger Institute and Agios, a pharmaceutical company in the USA, unveiled the long sought after genetic abnormality driving rare forms of diseases involving bone, known as Ollier disease or Maffucci syndrome. These non-hereditary diseases are characterised by multiple cartilaginous tumours arising in bone without and with haemangiomas (tumours of blood vessels) respectively. The number of tumours in each affected individual is variable, ranging from 2 to 100s, and may cause skeletal deformities at a young age. Although the majority of these tumours are benign, there is a 30 to 50% risk of malignant transformation into chondrosarcoma (a cancer formed by cartilage cells) during an affected individual’s lifetime. The genetic abnormality (mutation), which the research group has identified, that drives the growth of these cartilaginous tumours are found in the gene isocitrate dehydrogenase (IDH 1). The mutations are acquired early in the developing embryo which explains the distribution of multiple tumours in different tissues in the body. The research also explains the rare occurrence of a subtype of brain tumour, and leukaemia in patients with Ollier disease and Maffucci syndrome, as these two tumour types are also known to carry IDH1 mutations. Patients with cartilaginous tumours may benefit from the targeted therapy already being developed for these other tumours carrying these IDH1 and IDH2 mutations.

The research was largely funded by small UK charities - Skeletal Cancer Action Trust and Bone Cancer Research Trust




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13-16 10-2011

The UCL Cancer Institute, together with the Yale Cancer Centre and Karolinska University Hospital, held the 2nd 'Oncology at the Limits' conference in Stockholm.


An international panel of 32 world-renowned cancer researchers presented to oncologists from 26 countries the latest research breakthroughs in cancer genomics, personalised medicine and imaging. The conference was sponsored by Roche.

Oncologists from six sub-Saharan African countries were present, as well as representatives from other countries in the developing world.

All lectures will shortly be available on the Lancet website.

Patrick_Maxwell

Patrick Maxwell from UCL presents 'Targeting Hypoxia'

.

Tariq_Enver

Tariq Enver from the Cancer Institute listens to his presentation on 'Stem Cell in Cancer - Research at the Limits' being summarized by Professor Lothar Kanz (Germany)
.




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15-09-2011

The Debbie Fund ball held at the Hurlingham Club


The Debbie Fund ball held at the Hurlingham Club raised over £240,000 for debbie fund, thanks to the tremendous generosity of our supporters.

This funding will be used towards research conducted at the UCL Cancer Institute for cervical cancer. So far, in the short period since its creation in 2010, Debbie Fund has raised over £800,000 in the form of cash received and pledges. For more information visit the Debbie Fund web site.




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15-07-2011

Maternal smoking in pregnancy and birth defects: a systematic review based on 173 687 malformed cases and 11.7 million controls. Hackshaw A, Rodeck C, Boniface S (PudMed).


There is uncertainty over whether maternal smoking is associated with birth defects. We conducted the first ever comprehensive systematic review to establish which specific malformations are associated with smoking. METHODS Observational studies published 1959-2010 were identified (Medline), and included if they reported the odds ratio (OR) for having a non-chromosomal birth defect among women who smoked during pregnancy compared with non-smokers. ORs adjusted for potential confounders were extracted (e.g. maternal age and alcohol), otherwise unadjusted estimates were used. One hundred and seventy-two articles were used in the meta-analyses: a total of 173 687 malformed cases and 11 674 332 unaffected controls. RESULTS Significant positive associations with maternal smoking were found for: cardiovascular/heart defects [OR 1.09, 95% confidence interval (CI) 1.02-1.17]; musculoskeletal defects (OR 1.16, 95% CI 1.05-1.27); limb reduction defects (OR 1.26, 95% CI 1.15-1.39); missing/extra digits (OR 1.18, 95% CI 0.99-1.41); clubfoot (OR 1.28, 95% CI 1.10-1.47); craniosynostosis (OR 1.33, 95% CI 1.03-1.73); facial defects (OR 1.19, 95% CI 1.06-1.35); eye defects (OR 1.25, 95% CI 1.11-1.40); orofacial clefts (OR 1.28, 95% CI 1.20-1.36); gastrointestinal defects (OR 1.27, 95% CI 1.18-1.36); gastroschisis (OR 1.50, 95% CI 1.28-1.76); anal atresia (OR 1.20, 95% CI 1.06-1.36); hernia (OR 1.40, 95% CI 1.23-1.59); and undescended testes (OR 1.13, 95% CI 1.02-1.25). There was a reduced risk for hypospadias (OR 0.90, 95% CI 0.85-0.95) and skin defects (OR 0.82, 0.75-0.89). For all defects combined the OR was 1.01 (0.96-1.07), due to including defects with a reduced risk and those with no association (including chromosomal defects). CONCLUSIONS Birth defects that are positively associated with maternal smoking should now be included in public health educational materials to encourage more women to quit before or during pregnancy.

The story from the Guardian, read here.




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04-06-2011

PARP Inhibitor Improves Outcomes in Ovarian Cancer.


2011 — The experimental agent olaparib (AstraZeneca) might have a role to play in ovarian cancer. Results from a phase 2 trial have shown that it significantly prolonged progression-free survival in patients with platinum-sensitive relapsed serous ovarian cancer.

Patients who received olaparib as maintenance therapy achieved a progression-free survival that was nearly 4 months longer than those who received placebo, according to data presented at a press briefing held in advance of the American Society of Clinical Oncology (ASCO) 2011 Annual Meeting.

Median progression-free survival in the olaparib group was 8.4 months, compared with 4.8 months in the placebo group (hazard ratio [HR], 0.35; P < .00001). At the time of the analysis, 50% of olaparib group and 16% of the placebo group were still receiving treatment.


Dr. Jonathan Ledermann

This is the first randomized trial to demonstrate the benefits of a PARP inhibitor as maintenance therapy in platinum-sensitive relapsed serous ovarian cancer, which is the most common form of the disease, explained lead author Jonathan A. Ledermann, MD, professor of medical oncology at UCL Cancer Institute, University College London, United Kingdom.

Dream of Personalized Care

Mark G. Kris, MD, chair of ASCO's Cancer Communications Committee, noted that this trial is significant because "it fills an unmet need" for patients with relapsed ovarian cancer.

Olaparib lengthened the time that the disease could be controlled after the completion of active therapy, he explained, and allowed patients to return to a normal life.

The study also demonstrates the potential of targeted therapy. "That is our dream of personalized care, and this is one example of that dream approaching reality," Dr. Kris said.

Prof Jonathan Ledermann - Olaparib maintenance therapy for ovarian cancer and updates from ICON7 - video clip

Met Primary and Secondary End Points

Olaparib is an investigational poly (ADP ribose) polymerase (PARP) inhibitor that is currently being evaluated in phase 2 clinical studies for the treatment of certain types of ovarian and breast cancer. The results of 2 phase 2 trials, presented at the 2010 ASCO meeting and reported by Medscape Medical News at that time, demonstrated that olaparib produced significant response rates in patients with ovarian or breast cancer associated with BRCA1 or BRCA2 mutations. Responses in these nonrandomized trials were observed even in patients who had undergone 3 previous chemotherapy regimens and who had platinum resistance.

In the current study, Dr. Ledermann and colleagues examined 265 women with high-grade serous ovarian cancer who had received 2 or more previous platinum regimens and who had maintained partial or complete response after their last platinum-containing regimen. The women were randomized to oral olaparib 400 mg (n = 136) or placebo (n = 129).

The primary end point of the study was progression-free survival by RECIST; secondary end points included time to progression by CA-125 (GCIG criteria) or RECIST, overall survival, and safety.

"The study achieved its primary end point," said Dr. Ledermann. "This is a very significant difference — a 65% improvement with a highly significant value of 10–5."

Olaparib also significantly prolonged time to progression by CA-125 or RECIST (HR, 0.35; 95% confidence interval, 0.25 to 0.47; P < .00001). Median time to progression was 8.3 months in the olaparib group and 3.7 months in the placebo group. However, it is not yet known if there is an overall survival benefit; at the time of data cut-off, the data were too immature for analysis.

"The drug was very well tolerated, although there was an increase in 3 particular symptoms: nausea, fatigue, and vomiting," said Dr. Ledermann, pointing out that although these symptoms were seen in the placebo group, they were more common in the olaparib group.

Common adverse events included nausea (68% vs 35%), fatigue (49% vs 38%), vomiting (32% vs 14%), and anemia (17% vs 5%). The majority of events were grade 1 or 2, and the most frequently reported events of grade 3 or higher were fatigue (9 patients) and anemia (7 patients) in the olaparib group, and abdominal pain and fatigue (4 patients each) in the placebo group. A total of 31 patients (23%) in the olaparib group and 9 (7%) in the placebo group had both dose reductions and treatment interruptions.

This is the first study to demonstrate a statistically significant benefit of maintenance treatment for platinum-sensitive relapsed serous ovarian cancer, Dr. Ledermann concluded. "Further studies will be performed to determine the role of olaparib in the routine treatment of ovarian cancer."

In a statement, Jane Robertson, MBCHB, MD, medical science director at AstraZeneca, noted that these results are encouraging because "they suggest that olaparib may have a positive effect on progression-free survival in women with serous ovarian cancer, and may be a valuable therapeutic option for this aggressive form of cancer."




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04-06-2011

Astra drug slows ovarian cancer progression study


* Experimental drug olaparib is a PARP inhibitor
* Median progression-free survival 8.4 months for olaparib
* Median progression-free survival 4.8 months for placebo

By Bill Berkrot NEW YORK, May 18 (Reuters) - An experimental AstraZeneca (AZN.L) drug significantly delayed progression of a common and aggressive form of ovarian cancer in patients who had responded to chemotherapy, according to data to be presented at a major oncology meeting.
The drug, olaparib, which was tested in a Phase II trial as a so-called maintenance therapy, improved progression-free survival by almost four months in women who had already received at least two courses of platinum-based chemotherapy, according to data from an abstract, or brief summary, of the study released on Wednesday.
Those who received 400 milligrams of olaparib twice a day had a median progression-free survival, or the amount of time before the cancer returns or worsens, of 8.4 months. That compared with 4.8 months for patients who were taking a placebo. The results were considered by researchers to be highly statistically significant.

Results of the study, if confirmed in larger trials, could lead to use of olaparib to prevent recurrences or prolong remission in recurrent ovarian cancer. Many cancer drugs are now being tested as maintenance therapies, which could vastly increase sales of the medicines compared with use in a finite treatment regimen. "A well-tolerated antitumor agent that could be used for months or perhaps years as maintenance therapy after standard chemotherapy could be a big step forward and ultimately extend survival," Dr. Jonathan Ledermann, the study's primary investigator, said in a statement. Overall survival data was not yet available from the study, which included 265 patients with the most common form of ovarian cancer who had maintained a partial or complete response to chemotherapy.

The study will be presented next month at the American Society of Clinical Oncology meeting in Chicago. Side effects more common to olaparib than placebo included nausea, fatigue, vomiting and anemia.

Olaparib belongs to a class of drugs called PARP inhibitors that help kill cancer cells by blocking an enzyme important in repairing DNA damage. "My guess is that this drug, and drugs in its class, will find a very important place in prolonging remission in ovarian cancer," ASCO Chief Executive Dr. Allen Lichter told reporters on a conference call. (Reporting by Bill Berkrot, additional reporting by Julie Steenhuysen in Chicago).




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09-06-2011

UCL Cancer researcher leads landmark ovarian cancer study, read here.





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14-03-2011

Dr Chrissie Thirlwell: 1st prize for best science abstract



Dr Chrissie Thirlwell

Dr Chrissie Thirlwell won 1st prize for best science abstract for the second year running at the recent European Neuroendocrine Society meeting held in Lisbon, Portugal (9-11 March). The meeting was attended by a record 1600 delegates and more than 120 high quality abstracts were presented. Dr Thirlwell, who is a Cancer Research UK Clinician Scientist working within Prof Stephan Beck’s group, presented her work in which she has integrated DNA methylation and RNA expression analysis in pancreatic neuroendocrine tumours. Her results highlight the importance of the HIF/P53 pathway in tumour progression providing a rationale for therapeutic targeting of this pathway. Her work is partly funded by the Raymond and Beverly Sackler Foundation.

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14-03-2011

OncoTrack: A new European consortium launches search for novel genomic cancer diagnostics


Brussels, March 8th 2011 - OncoTrack, an international consortium of over 60 scientists, managed by Bayer HealthCare Pharmaceuticals and the Max Planck Institute for Molecular Genetics, has launched one of Europe's largest collaborative academic-industry research projects to develop and assess novel approaches for identification of new markers for colon cancer. The unique five year project, Methods for systematic next generation oncology biomarker development, brings together top scientists from European academic institutions with a wide range of expertise, and partners them with pharmaceutical companies.

In the last several decades, there have been significant advances made in the range of therapeutic agents available for the management of many common cancers. The inherent heterogeneity of most tumors, however, means that even innovative targeted therapies still typically only help a sub-population of patients. The challenges for the clinician of accurately diagnosing the tumour type and stage are further compounded by the necessity of predicting therapeutic responsiveness. Thus the application of tumor-specific biomarkers is recognized as a key factor in improving diagnosis, refining the selection of therapies and tracking the response of patients during treatment. A more sensitive, reproducible and systematic approach to the discovery and quantification of molecular markers reflecting neoplastic disease status, and their subsequent translation into clinically robust diagnostic methods, is therefore a prerequisite for the broad application of modern targeted therapies.

The essential objective of OncoTrack is to establish new methods for systematic next generation oncology biomarker development. Detailed molecular characterization of high quality tumor tissue will provide critical information to support our fundamental understanding of cancer and the influence of heterogeneity on response to colon cancer therapy. The project intends to generate high quality genomic and epigenetic sequence data from clinically well-defined tumors and their metastases, and will compare these to the germline genome of the patients. These data will be complemented by a detailed molecular characterization of the tumors. In parallel, the consortium will establish and characterize a novel series of xenograft tumor models and cell lines derived from the same set of tumors which will support research on tumor biology and also the early stages of biomarker qualification.

The combined data from all phases of the project will allow OncoTrack to address fundamental questions regarding the relationships between tumor genotype and phenotype, thus providing the starting point for discovery and selection of suitable candidates for development as biomarkers of colon cancer. Dr. David Henderson, Principal Scientist in Translational Sciences at Bayer HealthCare Pharmaceuticals, and Coordinator of the OncoTrack consortium, comments: 'OncoTrack is a prime example of the manner in which Public-Private Partnerships are breaking new ground in collaborative research involving academic and industrial partners. We have assembled a team of clinicians, molecular scientists, bioinformaticians and associated experts; thus creating a Europe-wide network of complementary capabilities extending far beyond the scope of a traditional 'one-on-one' industry-academic collaboration. The joint efforts of this consortium will generate the critical mass required to tackle the complex task of using large-scale genomic analysis as a basis for rational selection of novel cancer biomarkers.'
Prof. Hans Lehrach, Leader of the Managing Entity from the Max Planck Institute for Molecular Genetics comments: 'We welcome the unique opportunity afforded by this IMI initiative. The broad support from Europes' top pharma companies combined with the expertise within our Institute and our partners, will enable us to achieve the leverage necessary to tackle this complex project. Additionally the access to the scientists and commercial research facilities afforded by members of the OncoTrack Consortium will allow us to adopt avenues of discovery previously out of reach for academic research institutes. I look forward to our collaboration and feel that this initiative will both strengthen European academic research and provide our industry partners with important new tools applicable to clinical development programmes. Most importantly, our research will yield tangible benefits to patients in the therapy and management of their disease'.

The project Methods for systematic next generation oncology biomarker development, is partnered with a selected group of major global pharmaceutical companies, composed of AstraZeneca, Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim, Janssen Pharmaceutica, Merck, Pfizer and Roche Diagnostics, whose in-kind contributions to the project are matched by funding from the IMI Joint Undertaking, resulting in a total budget of €25.8mio.
The academic partners contribute essential skills & knowledge crucial toward the success of this enterprise. Those involved include: the Max Planck Institute for Molecular Genetics (Germany), Uppsala Universitet (Sweden), University College London (United Kingdom), Université Paris-Sud (France), Charité Universitätsmedizin Berlin (Germany), the Medizinische Universität Graz (Austria) and the Technische Universität Dresden (Germany). Aiding this ground-breaking project are three further pharmaceutical small and medium-sized enterprises (SME), International Prevention Research Institute (France), Experimental Pharmacology and Oncology and Alacris Theranostics (both in Germany) who will contribute to the success of OncoTrack, while the SME GABO:mi (Germany) will have the complex task of managing the multi-national project.

About the Innovative Medicines Initiative (IMI)

The project is funded by the Innovative Medicines Initiative, a young and unique public-private partnership between the pharmaceutical industry (represented by the European Federation of Pharmaceutical Industries and Associations, EFPIA) and the European Union (represented by the European Commission). IMI aims to put Europe at the forefront of biopharmaceutical innovation and to support more efficient discovery and development of better medicines for patients. IMI's innovative funding scheme has a budget of €1 billion from the European Union's 'Seventh Framework' Programme (FP7/2007-2013). That amount will be matched by in kind contributions of at least another €1 billion euro from the EFPIA member companies.





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09-01-2011

Spirogen Ltd. announces a research collaboration and license agreement with Genentech for the discovery and development of antibody drug conjugates


Spirogen Ltd, a leading oncology-focused companyd eveloping DNA sequence targeted agents, announced a multi-year research collaboration and license agreement with Genentech, a member of the Roche Group. The two companies will collaborate on the discovery and development of antibody drug conjugates (ADCs) as potential anticancer agents, using Spirogen's proprietary PBD drugs and associated linker technology.

Under the terms of the agreement, Spirogen will be primarily responsible for synthesizing and manufacturing drug reagents, while Genentech will use Spirogen's drug reagents to generate ADCs and evaluate their potential therapeutic utility. Genentech will have the exclusive license to fully develop and commercialize licensed products that contain these ADCs. Terms of the multi-year collaboration include an initial one-off license fee, development milestones on reaching pre-defined targets and further milestones and royalties for licensed products. "We are hopeful that this collaboration with Genentech will allow us to accelerate the development of ADCs based on our potent PBD drugs with one of the leading companies in the ADC field," said Christopher Martin, CEO of Spirogen. "We are pleased to enter into this collaboration with Spirogen," said James Sabry, M.D., Ph.D., Vice President of Genentech Partnering. "We believe ADCs have the potential to meaningfully impact the treatment of cancer. Genentech is committed to exploring the biology and clinical potential of ADCs in a variety of tumor types."

ABOUT SPIROGEN LIMITED
Spirogen is a privately-owned UK company, founded in 2001 by Professor David Thurston (now at the School of Pharmacy, University of London), Dr. Phillip Howard, Professor John Hartley (University College London) and Dr. Chris Martin. The company is pioneering the discovery and development of a unique class of low molecular weight sequence-specific DNA-interactive drugs designed to treat gene-mediated diseases. Spirogen's proprietary chemistry-based platform technology, based on the modification of members of a group of natural antibiotics called pyrrolobenzodiazepines (PBDs), forms the basis of a research effort that began over a decade ago to develop novel therapeutics with potential application in a number of markets. Spirogen's website is www.spirogen.com.





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16-12-2010

Non-coding RNAs and Cancer Symposium


Tuesday 12th April 2011, Beveridge Hall, University of London Senate House Registration deadline: 15th March 2011





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15-12-2010

Cancer: A variegated picture of leukaemia


Leukaemia-propagating cells and the cells derived from them are genetically heterogeneous, indicates a Nature study that has implications for targeted cancer therapy.
Analysing single cells from human B-cell acute lymphoblastic leukaemias (ALL), Mel Greaves and colleagues mapped the genetic heterogeneity of cells within a given tumour sample, the evolutionary path by which different subclones emerged and the ongoing dynamic changes associated with relapse. Subclones are genetically heterogenous and have complex evolutionary histories. The authors show that genetic changes within subclones are dynamic and change in the lead up to a diagnosis and in relapse.

The study also offers a plausible explanation for why advanced cancer is so difficult to treat, when the very cell that triggers the disease is itself genetically diverse and a moving target.





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26-11-2010

New single by Sarah Phillips in aid of the Debbie Phillips Fund



Sarah Phillips

Say It's Possible – the new single by Sarah Phillips in aid of the Debbie Phillips Fund is available now.

Order from Amazon

Download from iTunes







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11-10-2010

Hilary Calvert part of winning team


A team lead by Hilary Calvert, before he was recruited to UCL, won this years NCRN Translational Cancer Research Prize:

The story of the Newcastle PARP inhibitor study team's achievement begins in 1980 with an initial scientific observation by Dr Barbara Durkacz, a group leader at Newcastle University, that there was a poly-ADP ribosylation reaction, catalysed by a protein called PARP, associated with DNA damage. If this reaction was blocked, it increased the killing effect of the DNA damage on cancer cells.

In 1990, the newly formed Newcastle drug discovery team undertook its first project - the development of a PARP inhibitor. The team conducted the first ever clinical trial of a PARP inhibitor in cancer patients in 2003. Over the subsequent 20 years, the team has made significant contributions to compound identification, preclinical biology and testing, design of clinical trials and biomarkers and the subsequent clinical development of multiple compounds in this exciting new class of drugs.

This prize recognises the ability of this team to take a scientific concept through medicinal chemistry and preclinical work, right through to first-in-human clinical studies. All of this was done in a single location, with input from a wide range of research fields.

Today, PARP inhibitors are a major new therapeutic for cancer, including wormen with advanced breast cancer.





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18-10-2010

Reviving ‘tired’ immune cells gives blood cancer treatment a boost


UK researchers have discovered a way of improving the effectiveness of bone marrow transplantation, a key treatment for many patients with blood cancer, by providing an extra ‘boost’ to the immune system.

Each year in the UK, over 1000 patients receive blood or bone marrow transplants from a healthy donor as treatment for leukaemia or lymphoma. This therapy not only provides the patient with a new bone marrow but also a new immune system. This means that immune cells from the donor can attack the blood cancer, an effect called the ‘graft-versus-leukaemia’ effect. Killing residual blood cancer cells is a critical part of the transplant process and is almost certainly necessary to achieve cure.

The researchers from UCL ( University College London), together with collaborators at Harvard and Columbia Universities in the United States, examined why blood cancers come back in some patients who receive a transplant. In a study funded by the charity Leukaemia & Lymphoma Research, and published online in the Journal Of Clinical Investigation on the 18th October 2010, the scientists showed that cancer-targeting immune cells can become ‘worn out’ and stop working. This means that the graft-versus-leukaemia effect may be lost. Importantly, a new treatment can revive the ‘tired’ immune cells and get them to start working again.

By using clinically relevant mouse models of bone marrow transplantation, the researchers found that normal tissues outside the bone marrow were responsible for causing ‘exhaustion’ of the immune cells. This occurred because the normal cells have a molecule on their surface that eventually switches off the immune cells. They went on to show that treatment with an antibody could block this molecule and re-invigorate the immune system. Importantly, this could be done safely without any harmful side effects.

Dr. Ronjon Chakraverty, a bone marrow transplant physician at UCL who led the research team, said: ‘We have known for some time about the existence of the graft-versus-leukaemia response, but we didn’t understand why sometimes it doesn’t last. Our research helps to explain this failure and offers the potential of a new strategy to treat or prevent relapse of blood cancer in patients following bone marrow transplantation.’

Professor David Linch of the Cancer Institute at UCL, said: ‘These are exciting results, not only explaining why treatment may fail in some patients, but also paving the way towards improved therapy.’

Dr. David Grant, Scientific Director at Leukaemia & Lymphoma Research, said: ‘The more we understand about why bone marrow transplants can cure some patients but not others, the more we can use this form of treatment in the most effective way possible. This is a key discovery which will prevent many patients relapsing in the future.’





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11-10-2010

Top Cancer Specialists Receive ESMO Awards


The 2010 The European Society for Medical Oncology (ESMO) Lifetime Achievement Award will be presented to Professor Hilary Calvert who has long been involved in anticancer drug development. Prof Calvert is the Director of Anticancer Drug Discovery and Development at University College London Partners. The 2010 award to Prof Calvert was given in recognition for his seminal work on the introduction of carboplatin as a major anti-cancer agent and the development of a dosing formula based on its pharmacokinetics and its subsequent clinical use in ovarian cancer. "Prof Calvert is undoubtedly an international leader in his field", highlighted Prof Ian Smith, Chair of the ESMO Lifetime Achievement Award, "and his work has benefited countless patients around the world." The ESMO Lifetime Achievement Award is attributed to either an international research team or individual who have demonstrated commitment to cancer research treatment. It is supported by an unrestricted educational grant from GlaxoSmithKline.

In recent years Prof Calvert has worked on a program of drug development aimed at the use of molecular pathology of human cancer to define targets and develop drugs aimed at these targets. His research into the role of PARP inhibitors is leading to many developments in oncology as well as a variety of other diseases.

"We are in what is often called the 'post-genomic era'. This really means that we have amazing technologies that allow us to characterize gene expressions, mutations, translocations, etc., at an unprecedented rate. The excitement is that sometimes these are truly cancer specific changes and we can find or make drugs that exploit them. The challenge is that many of the most promising potential targets for drug design are regarded as intractable (or 'undruggable'). We need to develop techniques to approach these targets."

When asked which of his achievements has given him the most satisfaction, Prof Calvert replies: "This is hard to answer because there are so many more things to do. I think we achieved a good multidisciplinary team in Newcastle and established PARP inhibitors as a therapeutic class. However, I hope that the achievement that will give me the most satisfaction is yet to come!"





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26-04-2010

UCL-CI scientists discover ‘traitor’ human DNA helps viruses cause cancer


UCL scientists have discovered that stretches of human DNA act as a traitor to the body’s defences by helping viruses infect people and trigger cancer-causing diseases.

The research, which was undertaken at the UCL Cancer Institute and funded by Cancer Research UK, and published in Nature Cell Biology today, revealed that viruses can exploit the body’s DNA – dampening its antiviral immune response and allowing infection to take hold more easily.

more information...

ITN coverage...





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08-04-2010

ABC02 Trial


Finding new treatments for rare and hard to treat cancers is fundamental to cancer research.

Clinical trials are one of the best ways to test out new treatments and they do so by comparing the potentially better option with the standard treatment already available.

Our team of scientists have carried out the largest ever phase III clinical trial for advanced gall bladder and bile duct cancer which can’t be operated on.

Until now there has been no standard treatment for this group of cancer patients.

We set out to test whether patients with this type of cancer who were given both the chemotherapy drugs gemcitabine and cisplatin responded to treatment better than those patients who just received gemcitabine.

Over 400 patients in the UK took part. They were split in to two groups, one group were given a combination of the two drugs and the other had just gemcitabine. The treatment lasted for 24 weeks.

The findings have huge implications for treatment of advanced gall bladder and bile duct cancer. The combined drug treatment improved survival by a third. And the patients having this treatment lived on average over three months longer.

What’s exciting about our trial results here in the UK is that they have changed how treatment is given to patients in hospitals across the world.

The trial, called ABC02 was run by the Cancer Research UK and UCL Trials Centre.

Kate Law, director of clinical trials at Cancer Research UK, said: “Treating advanced gallbladder and bile duct cancer is very difficult and these results make us hopeful of adding precious extra months to a person’s life. We are committed to find new treatments for patients with rare and hard to treat cancers and hope these trial results will improve the way these cancers are treated across the world.”

The trial started in May 2005 and finished in September 2008.

The results were published today in the New England Journal of Medicine.

Dr John Bridgewater, co chief investigator of the ABC02 clinical trial and consultant oncologist at University College London Hospital is very pleased with the outcome.

Interview with John on MedpageToday

Additional information on this news story from UCL





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15-03-2010

Dr Chrissie Thirlwell and Dr Mohid Khan were each awarded first prize for best scientific and clinical research respectively at the recent European Neuroendocrine Tumour Society meeting in Berlin attended by around 1400 delegates. Neuroendocrine tumours are relatively rare but the Royal Free Hospital, under the leadership of Prof Martyn Caplin, has become one of the largest Neuroendocrine Centres in the world and recently was awarded the status of European Centre of Excellence, the first in the UK and one of only six in Europe.

Dr Thirlwell, a NIHR clinical lecturer in medical oncology, presented pioneering work on the epigenetics of NETs conducted in Prof Stephan Beck’s laboratory. In her preliminary work she has defined patterns of genome-wide promoter methylation for subgroups NET as well as developing a novel method for performing array based methylation analysis on paraffin embedded tissue. Dr Thirlwell s work is supported by the Raymond and Beverly Sackler Foundation (which also funds the Royal Free NET BioBank) and theWellcome Trust.

Dr Khan presented his data on the detection of circulating tumour cells (CTCs) in patients with NET performed in Dr Tim Meyer’s laboratory. CTCs have not previously been reported in NETs and Dr Kahn’s initial work suggests that their presence may be an important prognostic factor that will help to define therapy. Both projects were carried out in the UCL Cancer Institute and are the result of an increasingly productive collaboration between the Institute and the Royal Free NET unit.