Abstract
Poly (ADPribose) polymerase 1 (PARP-1) protein plays an important role in the repair of single strand breaks (SSBs) in the DNA. This is mediated by base excision repair (BER) of SSBs. PARP-1 inhibition allows accumulation of SSBs and consequently double strand breaks (DSBs). PARP inhibitors disrupt the BER and causes cell damage and death, especially in breast cancer susceptibility proteins 1 (BRCA 1) or BRCA2mutated cell in which homologous recombination (HR) pathway is defective. PARP-1 is effective as a single agent in BRCA-1 and BRCA-2 mutated ovarian and breast cancer. In addition, a number of studies have shown beneficial effects with PARP-1 inhibitors in combination with cytotoxic agents that target SSBs, especially in case of triple negative breast cancers (TNBC). Here we have reviewed potential clinical applications of PARP-1 inhibitors and issues associated with it for successful cancer chemotherapy.
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