Therapeutic potential of PARP inhibitors for metastatic breast cancer

摘要: Increasing understanding of the cellular aberrations inherent to cancer cells has allowed development therapies target biological pathways, an important step towards individualization breast therapy. The clinical poly(ADP-ribose) polymerase (PARP) inhibitors, with their novel and selective mechanism action, are example this strategy. PARP plays a key role in DNA repair mechanisms, particularly base excision pathway. Initially developed as inhibitors able enhance cytotoxicity radiation certain DNA-damaging agents, they have more recently been shown single-agent activity tumors. Inhibition repair-defective tumor can lead gross genomic instability cell death by exploiting paradigm synthetic lethality. Several studies evaluated for treatment cancer, context BRCA-mutated triple-negative cancers. In addition, inhibition PARPs functions chemotherapy-induced lesions potentiate effect some chemotherapy regimens. This article discusses current metastatic evidence from trials addresses its future implications.