A lack of oxygen (hypoxia) can make radiotherapy useless in the battle against cancer. How are we optimising treatment for patients with tumour hypoxia?
We developed and validated a gene signature, which characterises hypoxia status in head and neck cancer. Our research shows that cancer specific gene signatures are needed to identify hypoxic tumours. These signatures can then be used as biomarkers in personalised healthcare approaches that will improve survival. So far we have a phase III trial in head and neck cancer patients that is testing whether our signature can be used to select patients for treatment that targets hypoxia.
The next step is to establish early phase biomarker driven trials, in collaboration with our Informatics and Data Sciences, Biomarker Platforms and Rapid Translational Incubator colleagues, and established collaborations with pharmaceutical companies.
- Establishing gene signature biomarkers for bladder, prostate and lung cancer, and sarcoma (rare cancers that develop in the muscle, bone, nerves, cartilage, tendons, blood vessels and the fatty and fibrous tissues). An important aspect of our work will be to optimise the biomarkers/tests so that they can be used in the clinic.
- Working with researchers at The University of Manchester to undertake basic (laboratory based) research to increase our understanding of how hypoxia impacts on cell adhesion/invasion and how hypoxia could be targeted therapeutically.
Progress to date
- Gene signatures were derived and published for bladder and prostate cancers and sarcoma.
- Development and Validation of a 28-gene Hypoxia-related Prognostic Signature for Localized Prostate Cancer. EBioMedicine. 2018 May;31:182-189.
- Validation of a hypoxia related gene signature in multiple soft tissue sarcoma cohorts. Oncotarget. 2017 Dec 12;9(3):3946-3955.
- A Gene Signature for Selecting Benefit from Hypoxia Modification of Radiotherapy for High-Risk Bladder Cancer Patients. Clin Cancer Res. 2017 23:4761-4768.
- CR UK grant £299,171 over 3 years – West C, Choudhury A, Clarke N, Huddart R, Hussain S, James N, Yang L, Denley H. Validation of a biomarker for selecting radiotherapy combinations for muscle invasive bladder cancer patients.
- Complete work generating a gene signature for lung cancer.
- Complete work comparing different platforms for using the signatures in clinical trials.
- Design a biomarker driven trial using a signature.
- Begin work undertaking basic research to increase understanding of how hypoxia impacts on cell adhesion/invasion.
- Working with patient groups relating to our Musculoskeletal and Hearing Health research to understand particular benefits of PBT for them.