. Author manuscript; available in PMC: 2020 Nov 1.

Published in final edited form as: Nat Rev Mol Cell Biol. 2020 Feb 24;21(5):284–299. doi: 10.1038/s41580-020-0218-z

Table 2 |.

Mechanisms of resistance to PARP inhibitors in BRCA1-deficient cells and tumours

Mode of resistance	Mechanism	Refs
Restoration of BRCA1 function	Secondary mutations in BRCA1	^199,200
	Promoter demethylation	^201,202
	Promoter switch	²⁰²
Partial restoration of homologous recombination	Loss of 53BP1, RIF1, REV7, PTIP, DYNLL1 or the shieldin complex (BOX 2)	^{99–101,115, 122,186–189,197,} ^198,215,222
Restoration of replication fork stability	Loss of PTIP, SMARCAL1, ZRANB3 or HLTF	^147,148
Restoration of PARP signalling	Loss of poly(ADP-ribose) glycohydrolase (PARG)	¹⁹⁵
Other	Loss of SLFN11 (putative DNA/RNA helicase)	^191,203

BRCA1, breast cancer type 1 susceptibility protein; PARP, poly(ADP-ribose) polymerase.