Resistance to poly ADP-ribose polymerase inhibitors and its clinical implications

Abstract

Homologous recombination repair-deficient tumor cells including altered breast cancer gene 1 (BRCA1) and breast cancer gene 2 (BRCA2) tumor cells are known to respond to poly ADP-ribose polymerase (PARP) inhibitor through the mechanisms of reaching critical levels of genomic instability followed by mitotic catastrophe and ultimately synthetic lethality. PARP inhibitors are oral targeted drugs that are well tolerated and have received FDA approval for the treatment of ovarian, breast, pancreatic, and prostate cancer. The common challenge one encounters in clinical usage is the PARP inhibitor resistance, which may be de novo or acquired. In this review, various mechanisms underlying PARP resistance will be highlighted and the rationale to overcome the resistance.