BRCA1 Mutations May Predict Response to Treatment in Ovarian and Breast Cancers

BRCA1 Mutations May Predict Response to Treatment in Ovarian and Breast Cancers
Specific mutations in the BRCA1 gene may predict poor treatment responses in ovarian and breast cancer, according to two new studies published in The Journal of Clinical Investigation. Mutations in the BRCA1 gene are one of the most common risk factors for hereditary breast and ovarian cancers, as this protein is involved in a number of cellular processes, including DNA repair, cell cycle control, and regulates the expression of other genes. In fact, people with BRCA1 mutations exhibit an 80 percent to 90 percent lifetime risk of hereditary breast cancer, and 40 percent to 50 percent lifetime risk for hereditary ovarian cancer. Patients with such mutations often respond well to initial platinum-based therapy, and several PARP inhibitors currently under advanced-stage clinical investigation have proven beneficial in treating these people. But resistance to this treatment invariably arises, and is considered a major clinical challenge. One of the most common mechanism through which tumor cells develop resistance to such treatments is through secondary mutations in the BRCA1 and BRCA2 genes. The study "BRCA1185delAG tumors may acquire therapy resistance through expression of RING-less BRCA1," conducted by Netherlands Cancer Institute researchers, found that one of the most common BRCA mutation, BRCA1185delAG, gives rise to a protein that lacks a structural domain, called RING domain. Importantly, loss of the RING domain in both mice and human breast tumors predicted poor treatment responses, suggesting that the lack of this d
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