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 language | English |
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Pages (from-to) | 1102-1118 |
Number of pages | 17 |
Journal | Trends in Cancer |
Volume | 7 |
Issue number | 12 |
Early online date | 22 Sept 2021 |
DOIs | |
Publication status | Published - Dec 2021 |
Keywords
- base excision repair
- homologous recombination repair
- nucleotide metabolism
- poly(ADP-ribose) polymerase inhibitors
- therapy resistance