Tackling PARP inhibitor resistance

Kasper Fugger, Graeme Hewitt, Stephen C. West*, Simon J. Boulton

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

32 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1102-1118
Number of pages17
JournalTrends in Cancer
Volume7
Issue number12
Early online date22 Sept 2021
DOIs
Publication statusPublished - Dec 2021

Keywords

  • base excision repair
  • homologous recombination repair
  • nucleotide metabolism
  • poly(ADP-ribose) polymerase inhibitors
  • therapy resistance

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