Research progress in PARP inhibitors in breast cancer

Abstract

Individuals with breast cancer susceptibility genes(BRCA) germline mutations have a significantly increased lifetime risk for breast cancer, BRCA-mutant cancer cells have abnormal homologous recombination repair of DNA.Inhibition of Poly (ADP-ribose) polymerase (PARP) has shown marked benefit for breast cancer with homologous recombination deficiency, whether driven by defects in BRCA1, BRCA2, or other pathway components. Currently, under U. S.Food and Drug Administration approval of PARP inhibitor on ovarian cancer, clinical trials for PARP inhibitor are being conducted to assess whether PARP inhibitor as monotherapy or in combination with other drugs could benefit more breast cancer patients. Besides the studies of PARP inhibitor as monotherapy in breast cancer patients, researches in investigating platinum-PARP inhibitor combination in BRCA mutated breast cancer or triple negative breast cancer were conducted. In addition, many studies of immunotherapy combined with PARP inhibitor in breast cancer are ongoing. However, resistance to PARP inhibitors and the toxicity of the drugs remain challenges. This review will discuss the utility and unsolved problems of PARP inhibitor in breast cancer as well as the potential future directions. Key words: Breast neoplasms; Poly(ADP-ribose) polymerases; Enzyme Inhibitors; Research progress