Glioblastoma

Group members

• Dr Diego Ottaviani, NIHR Academic Clinical Fellow & Consultant in Medical Oncology
• Dr Nick Brown, Clinical Research Fellow & Specialist Registrar in Medical Oncology
• Dr Ben Kinnersley, Senior Research Fellow - Senior Computational Biologist
• Dr Vassilis Genoud, Senior Clinical Fellow 
• Dr Ariel Finkielsztein, Senior Research Fellow
• Max Reinstein, iBSc student

Research

Glioblastoma is the most common and aggressive primary malignant brain tumour. Due to the lack of effective treatment options, Cancer Research UK has included glioblastoma in the category of ‘cancers of substantial unmet need’. Our goal is to improve clinical outcomes for patients with glioblastoma, from pre-clinical development of novel therapies to early and later phase clinical trials.

Clinical trials

We have set up a national programme of immunotherapy clinical trials for patients with glioblastoma. We have recently completed recruitment for the IPI-GLIO trial (ISRCTN84434175) which is a phase II, open label, randomized study of ipilimumab (anti-CTLA monoclonal antibody) and temozolomide versus temozolomide alone after surgery and chemoradiotherapy in patients with recently diagnosed glioblastoma. We are currently actively developing new clinical trials.

Molecular mechanisms in glioblastoma

Alongside clinical trials, we are running a translational programme to improve our understanding of the molecular mechanisms driving glioblastoma response and resistance to treatment. There is emerging evidence that DNA organisation is critical in mediating responses to cancer treatment including chemotherapy and immunotherapy. We are characterising the DNA architecture in glioblastoma and how it can be modified to enhance treatment efficacy.

Selected publications

1. Liau LM, Ashkan K, Brem S ... Mulholland PJ, et al. Association of Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination With Extension of Survival Among Patients With Newly Diagnosed and Recurrent Glioblastoma: A Phase 3 Prospective Externally Controlled Cohort Trial. JAMA Oncol. 2023 Jan 1;9(1): 112-121.
2. Brown NF, Ottaviani D, Tazare J ... Mulholland P. Survival Outcomes and Prognostic Factors in Glioblastoma. Cancers (Basel). 2022 Jun 28;14(13): 3161.
3. Tesileanu CMS, Vallentgoed WR, Sanson M ... Mulholland PJ, et al. Non-IDH1-R132H IDH1/2 mutations are associated with increased DNA methylation and improved survival in astrocytomas, compared to IDH1-R132H mutations. Acta Neuropathol. 2021 Jun;141(6): 945-957.
4. Draaisma K, Tesileanu CMS, de Heer I ... Mulholland PJ, et al. Prognostic Significance of DNA Methylation Profiles at MRI Enhancing Tumor Recurrence: a Report from the EORTC 26091 TAVAREC Trial. Clin Cancer Res. 2022 Jun 1;28(11): 2440-2448.
5. Carter TJ, Agliardi G, Lin FY ... Mulholland P, Shevtsov M, Chester K. Potential of Magnetic Hyperthermia to Stimulate Localized Immune Activation. Small. 2021 Apr;17(14): e2005241.
6. Reardon DA, Brandes AA, Omuro A, Mulholland P, et al. Effect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma: The CheckMate 143 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Jul 1;6(7): 1003-1010.
7. Brown NF, Ng SM, Brooks C, Coutts T ... Mulholland P. A phase II open label, randomised study of ipilimumab with temozolomide versus temozolomide alone after surgery and chemoradiotherapy in patients with recently diagnosed glioblastoma: the Ipi-Glio trial protocol. BMC Cancer. 2020 Mar 12;20(1): 198.
8. Brown NF, Carter TJ, Ottaviani D, Mulholland P. Harnessing the immune system in glioblastoma. Br J Cancer. 2018 Nov;119(10): 1171-1181.
9. Brown NF, Williams M, Arkenau HT ... Mulholland P. A study of the focal adhesion kinase inhibitor GSK2256098 in patients with recurrent glioblastoma with evaluation of tumor penetration of [11C] GSK2256098. Neuro Oncol. 2018 Nov 12;20(12): 1634-1642. Erratum in: Neuro Oncol. 2020 Jun 9;22(6): 894.
10. van den Bent MJ, Klein M, Smits M ... Mulholland PJ, et al. Bevacizumab and temozolomide in patients with first recurrence of WHO grade II and III glioma, without 1p/19q co-deletion (TAVAREC): a randomised controlled phase 2 EORTC trial. Lancet Oncol. 2018 Sep;19(9): 1170-1179.
11. Liau LM, Ashkan K, Tran DD ... Mulholland P, Bosch ML. First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma. J Transl Med. 2018 May 29;16(1):142. Erratum in: J Transl Med. 2018 Jun 29;16(1):179.
12. Brown NF, Carter T, Kitchen N, Mulholland P. Dabrafenib and trametinib in BRAFV600E mutated glioma. CNS Oncol. 2017 Oct;6(4): 291-296.
13. Bardella C, Al-Dalahmah O, Krell D ... Mulholland P, et al. Expression of Idh1R132H in the Murine Subventricular Zone Stem Cell Niche Recapitulates Features of Early Gliomagenesis. Cancer Cell. 2016 Oct 10;30(4): 578-594.
14. Brown N, Carter T, Mulholland P. Adjuvant Chemotherapy is Indicated in Patients with Lower Grade Glioma. Clin Oncol (R Coll Radiol). 2017 Mar;29(3): 141-142.
15. Brown N, McBain C, Nash S ... Mulholland P. Multi-Center Randomized Phase II Study Comparing Cediranib plus Gefitinib with Cediranib plus Placebo in Subjects with Recurrent / Progressive Glioblastoma. PLoS One. 2016 May 27;11(5): e0156369.
16. Rampling R, Peoples S, Mulholland PJ, James A, et al. A Cancer Research UK First Time in Human Phase I Trial of IMA950 (Novel Multipeptide Therapeutic Vaccine) in Patients with Newly Diagnosed Glioblastoma. Clin Cancer Res. 2016 Oct 1;22(19): 4776-4785.