Hypoxia Biomarkers: Personalizing Cancer Treatments by Targeting Hypoxia

A hypoxic tumour microenvironment is a feature of solid tumours. Many tumour types contain high fractions of hypoxic tissue. The relationship between high levels of tumour hypoxia and a poor patient outcome (prognosis) is firmly established. Patients with the most hypoxic tumours have the worst prognosis and the tumours are more likely to spread to other sites in the body. The most hypoxic tumours are also more likely to recur following surgical removal and hypoxia leads to resistance to many treatments including radiotherapy, chemotherapy, and immunotherapy. Approximately 50% of solid tumours are hypoxic. Head and neck, prostate, bladder, and soft-tissue cancers are highly impacted by hypoxic microenvironments, and this reduces survival rates. Identification of patients for potential treatment with hypoxia targeted therapies could increase cancer survival rates by 30% in some patient populations, with hypoxia scoring required to make informed patient-specific treatment decisions. The use of precision medicine (treatment according to hypoxic-status) would reduce the need for trial-and-error approaches, improve patient outcomes, reduce the risk of exposure to cancer therapy complications while also improving cost-efficiency and patient quality-of-life.

Currently there is no easy, accurate, reproduceable way to clinically measure tumour hypoxia. To address this issue we have derived, developed, and validated a tissue specific test that can measure hypoxia by the expression of a number of hypoxia-associated genes – a signature. We developed signatures for different cancers (head and neck, prostate, bladder, sarcoma). The signatures, each made up of 24-28 genes, can be measured together in a single test (pan-cancer Next Generation Sequencing-NGS panel). 

The test is taken from the original diagnostic biopsy at the start of the cancer care pathway. The value of our test is to enable clinicians to make informed decisions on patient-specific precision treatment pathways according to tumour hypoxia-status.

Learning Objectives:

1. Define the impact of hypoxia on patient treatment response.

2. Explain the derivation, development and delivery of a hypoxia associated gene expression signature.

3. Evaluate the best clinical delivery route to improve cancer patient outcomes.