Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) represent the first medicines based on the targeting of the DNA damage response (DDR). PARPi have become standard of care for first-line maintenance treatment in ovarian cancer and have also been approved in other cancer indications including breast, pancreatic and prostate. Despite their efficacy, resistance to PARPi has been reported clinically and represents a growing patient population with unmet clinical need. Here, we describe the various mechanisms of PARPi resistance that have been identified in pre-clinical models and in the clinic.
Keywords: ATR; Homologous recombination repair (HRR); Hypomorphic mutants; Microhomology-mediated end joining; PARP inhibitor (PARPi) resistance; Polymerase theta; Replication stress; Reversion mutations; WEE1.
© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.