BRCA1 as a Therapeutic Target in Sporadic Epithelial Ovarian Cancer.
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 BRCA1 has evolved into a promising target for the treatment of sporadic disease and to outline the main potential small molecule inhibitors of BRCA1 in EOC.
Clark-Knowles
Katherine V
KV
Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON, Canada K1H 8L6.
O'Brien
Anna M
AM
Weberpals
Johanne I
JI