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Predicting synergistic drugs for recurrent GBM; finding better treatments, faster

Predicting synergistic drugs for recurrent GBM

1-year post-doctoral fellowship for a computational biologist from April 2016 to March 2017 (ongoing)

£ 44,539.01

Investigators:

Dr Michael Johnson DPhil (Oxon) FRACP FRCP
Reader in Genomic Medicine and Consultant Neurologist
Deputy Head, Centre for Clinical Translation, Division of Brain Sciences, Imperial College London

Dr Matthew Williams PhD MRCP
Consultant Clinical Oncologist and Hon. Senior Lecturer
Faculty of Medicine, Department of Surgery and Cancer, Imperial College London

Mr Kevin O’Neill MD FRCS
Consultant Neurosurgeon, Imperial College Healthcare NHS Trust

Dr Nelofer Syed PhD
Senior Research Fellow in Neuro-oncology
Division of Brain Sciences, Imperial College London

Lay summary: Glioblastoma (GBM) is an ultimately fatal brain tumour that inevitably recurs following surgery and chemoradiation resulting in death approximately 7 months after diagnosis. Here, we propose to utilize the molecular architecture of recurrent GBM to identify novel synergistic combinations of chemotherapy for patients with otherwise no effective treatment options. We will use publically available genomic datasets from paired primary and recurrent GBM to inform novel synergistic chemotherapeutic combinations from the large arsenal of already approved drugs with known pharmacology and safety data. Our method combines features of targeting gene networks and transcriptomic profiles, and builds on the successful application of our network methods for drug repurposing in epilepsy. We aim to identify combinations of drugs for GBM with strong synergy and low toxicity. We will confirm our synergistic predictions through experiment in the John Fulcher Laboratory, using existing funding and at no additional cost to this proposal. This 1-year project will:

(a) predict synergistic combinations of drugs for the treatment of recurrent GBM

(b) validate these predictions using in vitro models of GBM

(c) establish a computational infrastructure for precision medicine of recurrent GBM at Imperial College

(d) establish the scientific framework to leverage our results and developed technology to additional research funding from external funding agencies and/or technology investors