veliparib
Overview
Veliparib is an oral PARP1/2 inhibitor investigated in clinical trials for BRCA-mutated and HRD-positive solid tumors including breast, ovarian, lung, and pancreatic cancers.
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 encompasses olaparib, rucaparib, niraparib, and veliparib). 38% (11/29) had ≥6 months on therapy; all 10 long-responder BRCA2 tumors had biallelic inactivation, but 6/16 biallelic BRCA2-mutant tumors did not benefit, demonstrating that biallelic BRCA2 loss is necessary but not sufficient. PMID:39753968
- One PALB2 germline-pathogenic variant patient in the cohort received durable PARPi benefit, expanding the actionable HRD context beyond BRCA1/2. PMID:39753968
- Veliparib directly targets PARP1/PARP2; in BRCA1/2-wild-type mCRPC, resistance to PARP inhibitors (including veliparib) 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; additional determinants of HRD competence (beyond BRCA2 biallelic inactivation) remain to be defined. PMID:39753968
Cancer types (linked)
Sources
- PMID:39753968 — Zhu et al. 2024, MSK PDAC cohort (pdac_msk_2024); PARPi class outcomes in BRCA2-mutant and PALB2-mutant PDAC.
This page was processed by crosslinker on 2026-05-04. - PMID:28068672 — Yang et al., TRMT10A/USP10 axis in mCRPC; veliparib 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.