brca1 as a therapeutic target in sporadic epithelial ovarian cancerbrca1在零星的上皮卵巢癌治疗的目标.pdfVIP

Hindawi Publishing Corporation Journal of Oncology Volume 2010, Article ID 891059, 9 pages doi:10.1155/2010/891059 Review Article BRCA1 as a Therapeutic Target in Sporadic Epithelial Ovarian Cancer Katherine V. Clark-Knowles,1 Anna M. O’Brien,1 and Johanne I. Weberpals1, 2 1 Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON, Canada K1H 8L6 2 Division of Gynaecologic Oncology, The Ottawa Hospital, 501 Smyth Road, Ottawa, ON, Canada K1H 8L6 Correspondence should be addressed to Johanne I. Weberpals, jweberpals@ottawahospital.on.ca Received 2 June 2009; Accepted 23 November 2009 Academic Editor: Maurie M. Markman Copyright © 2010 Katherine V. Clark-Knowles et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In sporadic epithelial ovarian cancer (EOC), the inactivation of BRCA1 through various mechanisms is a relatively common event. BRCA1 protein dysfunction results in the breakdown of various critical pathways in the cell, notably, the DNA damage response and repair pathway. Tumors from patients with BRCA1 germline mutations have an increased sensitivity to DNA damaging chemotherapeutic agents, such as cisplatin, due to defective DNA repair. Thus, inhibiting BRCA1 in sporadic EOC using novel targeted therapies is an attractive strategy for the treatment of advanced or recurrent EOC. Several classes of small molecule inhibitors that affect BRCA1 have now been tested in preclinical and clinical studies suggesting that this is a rational therapeutic approach. The aim of this paper is to provide an understanding of how BRC