Grant: Project Grant

Solid tumours can contain cells that exist at lower oxygen levels than cells found in normal tissues. These poorly oxygenated (hypoxic) tumour cells are more difficult to kill using radiation or chemotherapy, and hypoxic tumour cells can spread (metastasize) to other tissues. Essentially, the tumour cells that are the most difficult to destroy during treatment are also the cells that make tumours more aggressive. Tumours also contain a variety of normal cells, including cancer-associated fibroblasts or CAFs. CAFs can produce protein fibres in the tumour that cause compression of tumour blood vessels and restrict blood flow, leading to decreased oxygen delivery to parts of the tumour. CAFs can therefore increase hypoxia in tumours, making the tumours less responsive to therapy. We recently found that a class of drugs normally used to reduce high blood pressure can block CAFs from producing these protein fibres, thereby changing the environment inside solid tumours to improve blood flow and reduce the number of hypoxic tumour cells. Armed with this therapeutic strategy, we are now interested in understanding how different types of CAFs influence the environment within solid tumours. We will investigate how CAFs contribute to hypoxia in several different tumour types including cervical cancer and head & neck cancer, and whether high blood pressure medications can improve response to radiation therapy. The work in this proposal will provide important new information about how cancer-associated fibroblasts influence the tumour environment and response to radiation therapy, and will lay a strong foundation for repurposing high blood pressure medications to design more effective treatment strategies for cancer patients.