Selecting Hypoxic Tumours for Treatment Modification


Select Team.pngThe study aims to check how much oxygen is in bladder cancer by looking at certain genes. These genes are connected to how much oxygen is in the cancer and are checked using tissue from a biopsy when someone is diagnosed. By doing genetic analysis, the study can find out oxygen levels within the cancer. This group has previously found that cancers with low oxygen levels respond well to a treatment called BCON. This research is crucial, it helps us see if we can measure oxygen levels in cancer and use this to change treatment. This could make treatments better for future patients.

Background: The BCON trial randomised patients to either radiotherapy or radiotherapy plus CON and reported significant improvement in local control (3-year rates 43% vs 54%, p=0.06) and overall survival (3-yr rates 46% vs 59%, p=0.04). The benefit of CON was maintained over long-term follow-up, 10-year overall survival was 30% (95% confidence interval [CI], 0.23-0.39) for patients who received radiotherapy plus CON and 24% (95% CI, 0.18-0.33) for the radiotherapy alone patients (hazard ratio [HR], 0.80; 95% CI, 0.61-1.04; p=0.08)1. The NICE guidelines2 recommend BCON as an option for treatment but recognise it's not optimal for oxygenated tumours, recommending research into biomarkers for treatment. There is a need to develop validated biomarkers which are feasible to implement in NHS practice to determine prognosis and inform selection of the most appropriate treatment option. Gene signatures are a set of genes associated with biology of cancers. We derived a 24-gene hypoxia signature for MIBC, that predicted benefit from giving CON with radiotherapy in a prospective analysis of a retrospective cohort3. This study will to determine our ability to receive and process tissue from multiple centres (The Christie, Lancaster Teaching Hospital and Rosemere Cancer Centre) for biomarker evaluation in a timely fashion, evaluating our analytic technique to endure it's fit for purpose in clinical settings. 

Objective: Establish a process to collect diagnostic tissue blocks and generate hypoxia signature scores in real-time to enable selection of hypoxia-targeting treatments.

Patient benefit: Identified biomarkers could be used for novel drug development targeting hypoxia-induced metastases, increasing overall patient survival for bladder cancer patients.

Project Lead:

Professor Ananya Choudhury, University of Manchester/The Christie NHS Foundation Trust

Professor Choudhury is currently Chair and honorary consultant in Clinical Oncology at The Christie NHS Foundation Trust from 2008, specialising in urology, with a strong interest in translational research and a focus on radiotherapy-related research in bladder and prostate cancers. Group leader of The Translational Radiobiology Group at the University of Manchester, which undertakes research to optimise and personalise radiotherapy using new techniques to deliver high doses of radiotherapy, while minimising side effects, and predictive imaging or tissue biomarkers to determine which patients benefit from different treatments.

Read about the other 2024 IOPP grant-awarded projects

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