PARP2
Overview
PARP2 (Poly(ADP-Ribose) Polymerase 2) is a member of the PARP family of DNA repair enzymes, functioning alongside PARP1 in detecting and signaling single-strand DNA breaks. PARP2 is a direct target of clinical PARP inhibitors including olaparib, rucaparib, niraparib, and talazoparib. Its inhibition, combined with homologous recombination deficiency, drives synthetic lethality in HR-deficient cancers.
Alterations observed in the corpus
- Direct target of olaparib/rucaparib/niraparib/talazoparib alongside PARP1; implicated in synthetic-lethal strategies for mCRPC tumors with BRCA1/2 pathway deficiency via the TRMT10A-USP10 HR-scaffold axis PMID:28068672
Cancer types (linked)
- Prostate cancer (PRAD): PARP2 inhibition is part of PARPi synthetic-lethal strategies studied in metastatic castration-resistant prostate cancer (mCRPC) PMID:28068672
Co-occurrence and mutual exclusivity
- Functions in parallel with PARP1 as a PARPi target; efficacy of PARP inhibition is modulated by TRMT10A/USP10 axis expression PMID:28068672
Therapeutic relevance
- Target of olaparib, rucaparib, niraparib, and talazoparib; synergy with USP10 inhibitor spautin-1 demonstrated in BRCA1/2-WT mCRPC cell line models PMID:28068672
Open questions
- Clinical importance of PARP2 vs PARP1 selectivity for different PARPi combinations in mCRPC remains to be defined.
Sources
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