UCL Cancer Institute


CRUK UCL Centre Development Fund

Cancer Research UK UCL Centre Development Fund Awards

The annual CRUK UCL Centre Development Fund provides short-term, pump-priming funding to support innovative research projects and inspirational, proof-of-concept cancer research. The scheme offers one year funding for up to £20,000 per award. Multidisciplinary applications are particularly encouraged.

The following projects have been selected for 2020 funding: 

Immune Landscape of hepatocellular carcinoma (HCC): B cells and tertiary lymphoid structures
Led by Professor Alberto Quaglia
UCL Cancer Institute
Co-applicants: Professor Teresa Marafioti, Professor Mala Maini

Project details

Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumour and is ranked as the sixth most commonly diagnosed malignant neoplasm and fourth most common cause of cancer-related death worldwide. Immunotherapy of HCC is gaining momentum and a better understanding of the HCC tumour immune microenvironment (TIME) is critical.

Some studies have investigated the role of individual cell types in the HCC TIME and their prognostic role, but results have been contradictory. High-resolution techniques such as multiplex immunohistochemistry, can improve our understanding of the HCC TIME by assessing multiple cell populations on the same sections, their co-localisation and relationship to cancer cells.

We plan to study HCCs surgically resected at the Royal Free London NHS Foundation Trust in collaboration with the surgical team led by Prof Brian Davidson. Multiplex immunohistochemistry will be performed using the technique established in the immune-onco Pathology laboratory (Group Leader Prof Teresa Marafioti). We will focus our attention on B lymphocytes and the presence, number and configuration of tertiary lymphoid structures (TLS). The number of mature and immature TLS will be correlated with clinical variables and measures of outcome. 

The results generated will provide vital preliminary information on the feasibility of using multiplex immunohistochemistry to examine the role of TLS in determining the prognosis and response to immunotherapy in HCC, aligning with existing expertise in liver immunotherapy (Prof Mala Maini and Prof Tim Meyer). A better understating of the immune response to HCC could ultimately inform on better patient stratification and selection for different immunotherapies, and our understanding of underlying immunopathogenesis to allow development of immunotherapies with novel mechanisms of action.

Correlating longitudinal changes in brain structure and function with the development of cognitive impairment in patients with limited-stage small cell lung cancer (LS-SCLC) following prophylactic cranial irradiation (PCI): a PETfMRI study
Led by Professor Siow Ming Lee and Dr James Wilson
UCL Cancer Institute
Co-applicant: Professor Francesco Fraioli

Project details

This study aims to characterise neuroanatomical and functional changes in the brains of patients with limited-stage small cell lung cancer (LS-SCLC) caused by prophylactic cranial irradiation (PCI). Changes in patients’ brain imaging will be correlated with neurocognitive test scores and quality of life assessments to identify which changes or baseline imaging characteristics are correlated with neurocognitive decline or changes in quality of life. This is the first study to perform longitudinal 18F-Fluorodeoxyglucose-positron emission tomography/functional MRI in this patient group. Similarities in imaging characteristics with well described dementia syndromes will be sought in the hope of uncovering potential therapeutic targets to prevent cognitive decline following PCI and therefore improve patient uptake of PCI which been shown to improve survival and reduce the incidence of clinically significant brain metastases.

Plasma DNA for early detection of treatment inefficacy in advanced prostate cancer patients: a three-stage biomarker study integrated in the multi-centre STAMPEDE clinical trial
Led by Professor Gert Attard
UCL Cancer Institute
Co-applicants: Dr Louise Brown

Project details

Optimising the first treatment a man with advanced prostate cancer receives results in significant improvements in life expectancy and disease remission. However, despite several new treatments recently receiving approval or initiating evaluation in trials, physicians have no good way to ascertain whether a treatment is ineffective and change it for or add on something better.

We have developed a test that detects traces of prostate DNA in plasma (ctMethSig). We hypothesise that a treatment is ineffective if prostate DNA has not regressed from blood after 4-16 weeks treatment. With this funding, we will subject plasma DNA to bisulfide next-generation sequencing and extract methylation data to define whether tumour DNA is present. In collaboration with Louise Brown at the MRC CTU at UCL, we will do this in a cohort of 40 men recruited to the STAMPEDE multicentre national clinical trial and from whom we collected blood between 2016 and 2018. We will formally assess whether ctMethSig positive men are more likely to relapse within 18 months. This will constitute stage I clinical qualification in the CRUK biomarker road-map for ctMethSig and support prospective validation of the test in the PARADIGM trial, currently being conducted by the UCL Cancer Trials Centre.

Imaging therapy response in patient-derived colorectal organoids
Led by Professor Tony Ng
UCL Cancer Institute
Co-applicants: Professor Daniel Hochhauser, Dr Manuel Rodriguez-Justo, Dr Paul Barber

Project details

Colorectal cancer (CRC) is one of the most common malignancies and presents limited treatment options in the metastatic setting. Until recently, conventional chemotherapy such as FOLFOX or FOLFIRI formulated the backbone of treatment for all cases with modest response rates. Targeted therapies including the epidermal growth factor receptor (EGFR) monoclonal antibodies cetuximab and panitumumab, and immune checkpoint inhibitors have also been incorporated recently.

The objectives of the study focus on gaining a better understanding on the impact of EGFR-targeted therapy (cetuximab), immunotherapy (nivolumab) and conventional chemotherapy on immune (T-cell) infiltration. By assessing that in patient-derived organoids, we expect the knowledge to be rapidly translated into the clinical setting. 

The potential translational impacts of the project are to prognosticate the patient response to cetuximab and chemotherapy treatment and evaluate the potential additional therapeutic benefits of combining immune checkpoint inhibitors with cetuximab and chemotherapy in a patient stratification algorithm based on organoid imaging.

Towards a CAR T-cell therapy approach for Calreticulin mutated myelofibrosis
Led by Dr Martin Pule
UCL Cancer Institute

CRUK UCL Centre Development Funds success story:

One of the first CRUK UCL Centre Development Funds, awarded in 2011 has contributed to a recent Cancer Cell publication on the molecular signatures of regression of the canine transmissible venereal tumor (CTVT) by Professors Ariberto Fassati (Division of Infection & Immunity) and Stephan Beck (UCL Cancer Institute). This study used global transcriptional, methylation, and functional pathway analyses on serial biopsies of vincristine-treated CTVTs. By comparing CTVTs that regressed to CTVTs that did not regress after vincristine treatment,  they found that regression occurs in sequential steps, starting with an acute inflammation. The chemokine CCL5, which attracts immune cells into the tumour site, was identified as a possible driver of CTVT regression and changes in gene expression were associated with methylation changes at specific intragenic sites. These results underscore the critical role of host innate immunity in triggering cancer regression.