Therapeutic targeting of BRCA1-mutated breast cancers with agents that activate DNA repair.

ABSTRACT: Cancers due to germline mutations in the BRCA1 gene tend to lack targets for approved chemoprevention agents. This study aimed at a targeted chemoprevention strategy for BRCA1-associated malignancies. Mutant BRCA1 limits the base-excision DNA repair activity that addresses oxidative DNA damage, the accumulation of which heightens one's risk for cancer. Therefore, we conducted a high-throughput chemical screen to identify drug candidates that could attenuate the inhibitory effects of mutant BRCA1 on this repair activity, thereby describing a new class of DNA repair-activating chemopreventive agents. In the screen design, such drugs functioned by enhancing base-excision DNA repair of oxidative DNA damage in the presence of mutant BRCA1, with minimal cytotoxicity. We identified at least one n

SUBMITTER: Alli E 

PROVIDER: S-EPMC4388430 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature