rucaparib

Overview

Rucaparib is an oral PARP1/2 inhibitor with FDA approval for germline BRCA1/2-mutant advanced ovarian cancer and BRCA1/2-mutant castration-resistant prostate cancer. In pancreatic cancer, PARPi including rucaparib are used in patients with homologous recombination deficiency.

Evidence in the corpus

  • The MSK PDAC 2024 cohort (n=2,336) analyzed outcomes in n=29 stage-IV patients who received a PARPi (class includes rucaparib, olaparib, niraparib, veliparib). 38% (11/29) had ≥6 months on therapy; 10/11 long-responders had biallelic BRCA2 mutations. However, 6/16 BRCA2-mutant tumors with biallelic loss did not benefit, indicating biallelic BRCA2 loss is necessary but not sufficient for durable PARPi response. PMID:39753968
  • One BAP1 loss-of-function fusion tumor (BRCA1/2 wild-type, MAPK-WT) also received durable PARPi benefit, pointing to broader HRD beyond BRCA1/2 as a predictive context. PMID:39753968
  • Rucaparib directly targets PARP1/PARP2; in BRCA1/2-wild-type mCRPC, resistance to PARP inhibitors (including rucaparib) may be driven by high TRMT10A expression, which supports BRCA1 recruitment to DNA double-strand breaks via ATM-mediated Ser28 phosphorylation PMID:28068672

Resistance mechanisms

  • Biallelic BRCA2 loss is necessary but not sufficient for PARPi response in PDAC; undetermined co-occurring molecular features define the responsive subset. PMID:39753968

Cancer types (linked)

Sources

This page was processed by crosslinker on 2026-05-04. - PMID:28068672 — Yang et al., TRMT10A/USP10 axis in mCRPC; rucaparib named as PARPi class member; high TRMT10A expression tracks with PARPi resistance across the class.

*This page was processed by entity-page-writer on 2026-05-15.