Development and implementation of precision therapies targeting base-excision DNA repair in BRCA1-associated tumors

ABSTRACTIntroduction: The association between deleterious BRCA1 mutations and increased risk of breast, ovarian, fallopian tube, pancreatic, prostate and stomach cancers is well-defined.Areas covered: Defects in the repair of DNA damage will result in a single strand or double strand break and genomic instability. In turn, mutations will occur, significantly increasing the risk of cancer. This review focuses on BRCA1 and the evolving precision therapies associated with BRCA1-associated tumors. Emerging evidences suggest that targeting different pathways of DNA damage repair is a promising new approach.Expert opinion: Although the role of PARP inhibitors in BRCA1 mutated breast or ovarian cancer is well-established, their potential role in tumors with either somatic mutations or homologous recombination repair deficiency is yet to be fully defined. Ongoing clinical trials will hopefully address this critical clinical issue. Inhibitors of ATR and ATM are also currently entering into early phase clinical tri...