Affected individuals with harmful genetic change (mutations) in BRCA1 have a greatly increased risk (10-40 times higher than people without mutations) of developing breast and ovarian cancers. Furthermore, the majority (approximately 70%) of breast cancers with BRCA1 mutations do not response to advanced cancer treatments (e.g., targeted drugs) and develop resistance to the traditional chemotherapy/radiotherapy quickly, thus display very aggressive tumor behavior with a poor prognosis. As such, there is an urgent need for learning more about cancers with BRCA1 mutations, particularly the triple negative breast cancers, and finding better treatments for these patients. BRCA1 has been well doc...

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Affected individuals with harmful genetic change (mutations) in BRCA1 have a greatly increased risk (10-40 times higher than people without mutations) of developing breast and ovarian cancers. Furthermore, the majority (approximately 70%) of breast cancers with BRCA1 mutations do not response to advanced cancer treatments (e.g., targeted drugs) and develop resistance to the traditional chemotherapy/radiotherapy quickly, thus display very aggressive tumor behavior with a poor prognosis. As such, there is an urgent need for learning more about cancers with BRCA1 mutations, particularly the triple negative breast cancers, and finding better treatments for these patients. BRCA1 has been well documented as a pivotal suppressor of breast and ovarian cancers, and a lot of studies have revealed its involvement in many biological processes, especially in protecting our genetic material from damage caused by sunlight and other exposures. However, we do not yet have a full understanding how BRCA1 performs its functions in suppressing tumor formation at the molecular level and what are the adverse effects resulted from BRCA1 mutations found in cancer patients. This poses a huge challenge for patient counseling, determining prevention strategies, and the formulation of treatment plans when disease strikes. Here, we describe a research project to study the key functions of BRCA1 in great details to fill this knowledge gap. This is now possible because we have developed robust systems to obtain highly quality protein preparations and robust stable cell lines for mechanistic workup. The critical information gained from the study will help us to explain why and which mutations in BRCA1 will cause cancers, and will provide the foundation for formulating new treatment regimens that are more effective and specific than current ones.

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