Tackling PARP inhibitor resistance
Abstract
Homologous recombination-deficient (HRD) tumours, including those harbouring mutations in the BRCA genes, are hypersensitive to treatment with inhibitors of poly(ADP-ribose) polymerase (PARPis). Despite high response rates, most HRD cancers ultimately develop resistance to PARPi treatment through reversion mutations or genetic/epigenetic alterations to DNA repair pathways. Counteracting these resistance pathways, thereby increasing the potency of PARPi therapy, represents a potential strategy to improve the treatment of HRD cancers. In this review, we discuss recent insights derived from genetic screens that have identified a number of novel genes that can be targeted to improve PARPi treatment of HRD cancers and may provide a means to overcome PARPi resistance.
Journal details
Journal Trends in Cancer
Volume 7
Issue number 12
Pages 1102-1118
Available online
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Publisher website (DOI) 10.1016/j.trecan.2021.08.007
Europe PubMed Central 34563478
Pubmed 34563478
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