Table 2.

Potential mechanisms of resistance to PARP inhibitors

Potential mechanisms of resistance	Potential treatment
Restoration of HRD
Secondary reversion mutations in HRD genes49–52	–
Loss of 53BP154,55	HSP90 inhibitor59
Replication fork protection57,60	Topoisomerases inhibitor61
Alteration in cell cycle regulation
Increased expression of Wee162	Wee1 inhibitor62,63
ATM/ATR pathway activation64	ATM/ATR inhibitors65
Drug efflux
Upregulation of p-glycoprotein66	Next generation PARP inhibitor67
Activation of other pathways
PI3K/AKT68	PI3K inhibitors69
MET70	MET inhibitors70

Note: Dash indicates not reported.

Abbreviations: HRD, homologous recombination; 53BP1, p53 binding protein 1; HSP90, heat shock protein 90; PI3K, phospholnositide-3 kinase; PARP, poly (ADP-ribose) polymerase.