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Reviews

BRCA1 at the crossroad of multiple cellular pathways: approaches for therapeutic interventions

Laboratory of Genomic Applications, Department of Surgical Oncology, Sheba Medical Center, Tel-Hashomer, Israel

Requests for reprints: Ronit I. Yarden, Laboratory of Genomic Applications, Department of Surgical Oncology, Sheba Medical Center, Tel-Hashomer 52621, Israel. Phone: 972-3-530-5868; Fax: 972-3-530-5868. E-mail: ronit.yarden{at}sheba.health.gov.il

Approximately 10% of the cases of breast cancer and invasive ovarian cancer are hereditary, occurring predominantly in women with germ-line mutations in the BRCA1 or BRCA2 genes. Low expression of these genes in sporadic tumors extends their significance to sporadic breast and ovarian cancers as well. For over a decade since its identification, extensive research has been directed toward understanding the function of the breast and ovarian tumor suppressor gene BRCA1. The long-term goal has been to identify the biochemical pathways reliant on BRCA1 that can be exploited for developing targeted therapies and benefit mutation carriers. To date, no one specific role has been identified, but rather it is clear that BRCA1 has significant roles in multiple fundamental cellular processes, including control of gene expression, chromatin remodeling, DNA repair, cell cycle checkpoint control, and ubiquitination, and overall is important for maintenance of genomic stability. Major findings and potential BRCA1-dependent therapies will be discussed. [Mol Cancer Ther 2006;5(6):1396–404]

Received 11/14/05; revised 3/ 4/06; accepted 4/21/06.