Role of BRCA2 in the response to replication inhibitors

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Some cancer patients have specific genetic defects in their cancer cells that influence their response to anti-cancer treatment. Patients with cancers such as breast and pancreatic cancer can have mutations in the BRCA2 gene, which makes their cancer cells less able to repair damage in their chromosomal DNA. This is important for therapy because many anti-cancer treatments work by causing deadly damage to the DNA. Patients with and without mutations in BRCA2 do therefore respond differently to some of these treatments. DNA-damaging drugs include agents called replication inhibitors such as Gemcitabine, which are used for chemotherapy of breast and pancreatic cancer. How cancer cells with BRCA2 mutations respond to replication inhibitors is not well understood. This project aims to characterise how BRCA2 prevents and repairs DNA damage in cells treated with replication inhibitors to generate new insights into the treatment response in genetic backgrounds frequently found in cancer patients.