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BRCA1 and the Cellular Response to Chemotherapy

Germline mutations in the BRCA1 gene account for approximately 5% of breast and ovarian cancers, and lower than normal BRCA1 expression may be an important factor contributing to sporadic cancers. BRCA1 responds to damaged DNA by participating in DNA repair pathways, mRNA transcription, cell cycle regulation, and protein ubiquitination. Because most chemotherapeutic agents either directly or indirectly damage DNA, the association between BRCA1 activity and chemotherapy-induced DNA damage has been investigated. Kennedy et al. (p. 1659) review the evidence that the level of BRCA1 function in an individual patient can guide the type of chemotherapy used to treat breast and ovarian cancer. They conclude that current evidence indicates that loss of BRCA1 function in cancers may be associated with sensitivity to DNA-damaging chemotherapy and may also be associated with resistance to spindle poisons. They recommend that prospective clinical studies be conducted to investigate the role of BRCA1 in the response to chemotherapy.