# PARP

Source: https://onco.cc/targets/parp/  
OnCo record `parp` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

PARP is a DNA repair enzyme. Cancers that have already lost one repair system (BRCA) die when this second one is blocked; healthy cells survive.

## Summary

PARP inhibitors (olaparib, niraparib, rucaparib, talazoparib) exploit synthetic lethality with BRCA1/2 mutations and homologous recombination deficiency in ovarian, breast, prostate, and pancreatic cancer. Olaparib is approved in adjuvant germline-BRCA breast cancer (OlympiA). PARP1-selective inhibitors (saruparib) and PARP PET tracers are the next step.

## Fields

- Kind: Target
- Last checked: 2026-09-04
- Also known as: PARP1/2; Poly [ADP-ribose] polymerase 2
- Tags: synthetic-lethality
- Symbol: PARP1
- Class: enzyme
- Biology: Poly(ADP-ribose) polymerase 1 senses single-strand breaks; trapping on DNA is the key cytotoxic mechanism.
- Where found: BRCA/HRD ovarian, breast, prostate, pancreatic cancers

## Notes

- Prostate cancer: four approved routes with four different eligibility gene lists, from BRCA2 alone through BRCA1 and BRCA2 to 12 and 14 gene panels, and response concentrated in BRCA2 (56% objective response in PROfound against 10% for ATM and 6% for CDK12). Resistance is usually reversion of the qualifying gene, found multiclonally in cell-free DNA (Quigley 2017).

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/PARP_inhibitor
- Wikipedia: https://en.wikipedia.org/wiki/PARP_inhibitor

## Connected records

- cancers: [Basal-like 1 triple-negative breast cancer (BL1)](https://onco.cc/cancers/tnbc-basal-like-1/), [BRCA-associated triple-negative breast cancer](https://onco.cc/cancers/brca-associated-tnbc/), [Ewing sarcoma](https://onco.cc/cancers/ewing-sarcoma/), [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Male breast cancer](https://onco.cc/cancers/male-breast-cancer/), [Metastatic castration-resistant prostate cancer](https://onco.cc/cancers/prostate-mcrpc/), [Ovarian cancer](https://onco.cc/cancers/ovarian/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Prostate cancer](https://onco.cc/cancers/prostate/), [Small-cell lung cancer](https://onco.cc/cancers/sclc/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/), [Uterine sarcoma](https://onco.cc/cancers/uterine-sarcoma/)
- drugs: [BRACAnalysis CDx](https://onco.cc/drugs/bracanalysis-cdx/), [Iniparib](https://onco.cc/drugs/iniparib/), [myChoice CDx](https://onco.cc/drugs/mychoice-cdx/), [Niraparib](https://onco.cc/drugs/niraparib/), [Olaparib](https://onco.cc/drugs/olaparib/), [Palacaparib](https://onco.cc/drugs/palacaparib/), [Rucaparib](https://onco.cc/drugs/rucaparib/), [Saruparib](https://onco.cc/drugs/saruparib/), [Senaparib (IMP4297)](https://onco.cc/drugs/imp4927/), [Talazoparib](https://onco.cc/drugs/talazoparib/), [Veliparib](https://onco.cc/drugs/veliparib/)
- pathways: [Androgen receptor signalling](https://onco.cc/pathways/ar-signaling/), [Base excision repair, PARP & alkylation damage](https://onco.cc/pathways/base-excision-repair-parp/), [cGAS-STING innate sensing](https://onco.cc/pathways/cgas-sting/), [Clonal haematopoiesis (CHIP)](https://onco.cc/pathways/clonal-haematopoiesis/), [DNA damage response & homologous recombination](https://onco.cc/pathways/ddr/), [DNA replication stress](https://onco.cc/pathways/replication-stress/), [Double-strand break repair: HR versus end joining](https://onco.cc/pathways/homologous-recombination-repair/), [Mutagenesis & mutational signatures](https://onco.cc/pathways/mutagenesis-signatures/), [Pancreatic cancer (KEGG map)](https://onco.cc/pathways/pancreatic-cancer-signalling/), [Synthetic lethality: paired dependencies](https://onco.cc/pathways/synthetic-lethality-map/)
- key papers: [Analysis of circulating cell-free DNA identifies multiclonal heterogeneity of BRCA2 reversion mutations associated with resistance to PARP inhibitors](https://onco.cc/key-papers/paper-quigley-brca2-reversion-cfdna-parp-resistance-cancer-discov-2017/), [OlympiA: a year of olaparib after surgery for BRCA-mutated, high-risk early breast cancer](https://onco.cc/key-papers/paper-olympia-nejm-2021/), [PAOLA-1: olaparib added to bevacizumab maintenance in newly diagnosed ovarian cancer, with benefit confined to HRD-positive tumours](https://onco.cc/key-papers/paper-paola-1-nejm-2019/), [PROfound: olaparib for metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations](https://onco.cc/key-papers/paper-profound-nejm-2020/), [SOLO-1: two years of olaparib maintenance after first-line chemotherapy for BRCA-mutated ovarian cancer](https://onco.cc/key-papers/paper-solo-1-nejm-2018/), [TRITON2: rucaparib in men with metastatic castration-resistant prostate cancer harbouring a BRCA1 or BRCA2 alteration](https://onco.cc/key-papers/paper-abida-triton2-rucaparib-brca-jco-2020/)
- trials: [ATHENA-MONO / GOG-3020](https://onco.cc/trials/athena-mono/), [BROCADE3](https://onco.cc/trials/brocade3/), [DUO-E / GOG-3041 / ENGOT-EN10](https://onco.cc/trials/duo-e/), [DUO-O / ENGOT-ov46](https://onco.cc/trials/duo-o/), [EMBRACA](https://onco.cc/trials/embraca/), [OlympiAD](https://onco.cc/trials/olympiad/), [PAOLA-1 / ENGOT-ov25](https://onco.cc/trials/paola-1/), [PHOENIX DDR/Anti-PD-L1](https://onco.cc/trials/phoenix/), [POLO](https://onco.cc/trials/polo/), [PRIMA / ENGOT-OV26](https://onco.cc/trials/prima/), [PROfound](https://onco.cc/trials/profound/), [SOLO-1](https://onco.cc/trials/solo-1/), [TALAPRO-2](https://onco.cc/trials/talapro-2/), [TRITON3](https://onco.cc/trials/triton3/)
- ideas: [A functional test for homologous recombination deficiency validated across laboratories](https://onco.cc/ideas/idea-tr2-hrd-functional-standard/), [A synthetic lethality map for every cancer driver in every tissue context](https://onco.cc/ideas/idea-moon-synthetic-lethality-map-every-driver/), [Subtype-directed therapy for SCLC (ASCL1 / NEUROD1 / POU2F3 / inflamed)](https://onco.cc/ideas/idea-sclc-subtype-directed/), [Which patients' blood clones will become leukaemia after treatment?](https://onco.cc/ideas/idea-chip-risk-modifiers/)
- pairings: [PARP inhibitor + bevacizumab maintenance (HRD-positive)](https://onco.cc/pairings/parp-plus-bevacizumab/)
- terms: [BRCA reversion mutations](https://onco.cc/terms/brca-reversion-mutations/), [Checkpoint (two meanings)](https://onco.cc/terms/checkpoint/), [Enabling characteristic: genome instability and mutation](https://onco.cc/terms/genome-instability-mutation/), [Enzyme](https://onco.cc/terms/enzyme/), [Homologous recombination deficiency (HRD)](https://onco.cc/terms/hrd/), [Homologous recombination deficiency (HRD) in breast cancer](https://onco.cc/terms/hrd-in-breast-cancer/), [Small-cell lung cancer transcription-factor subtypes (SCLC-A, SCLC-N, SCLC-P, SCLC-I) and SLFN11](https://onco.cc/terms/sclc-molecular-subtypes/), [Tumour suppressor gene](https://onco.cc/terms/tumour-suppressor-gene/), [Who is eligible for a PARP inhibitor in prostate cancer, and why the gene matters](https://onco.cc/terms/prostate-hrr-eligibility/)
- roadmaps: [Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question](https://onco.cc/roadmaps/pancreatic-roadmap/)
- biomarkers: [Homologous recombination repair gene mutation in prostate cancer](https://onco.cc/biomarkers/hrr-gene-mutation/)
- technologies: [HRD & BRCA testing](https://onco.cc/technologies/hrd-testing/), [HRD genomic scar scores (GIS, LOH, HRDetect)](https://onco.cc/technologies/hrd-genomic-scar-scores/), [PARP inhibitors](https://onco.cc/technologies/parp-inhibitor/), [PARP PET](https://onco.cc/technologies/parp-pet/), [RAD51 foci assay (functional HRD test)](https://onco.cc/technologies/rad51-foci-assay/), [Radioligand plus DNA-repair inhibitor combinations](https://onco.cc/technologies/radionuclide-parp-combination/), [Synthetic lethality approaches](https://onco.cc/technologies/synthetic-lethality-approaches/)
- institutions: [Abramson Cancer Center, University of Pennsylvania](https://onco.cc/institutions/penn-abramson/), [Newcastle Cancer Centre / Northern Centre for Cancer Care](https://onco.cc/institutions/newcastle-cancer-centre/), [Sheba Medical Center](https://onco.cc/institutions/sheba/), [Stephenson Cancer Center, OU Health](https://onco.cc/institutions/stephenson-oklahoma/)
- people: [Alan Ashworth](https://onco.cc/people/alan-ashworth/), [Alan D. D'Andrea](https://onco.cc/people/alan-dandrea/), [Amit M. Oza](https://onco.cc/people/amit-oza/), [Andrew Tutt](https://onco.cc/people/andrew-tutt/), [Charles E. Geyer Jr.](https://onco.cc/people/charles-geyer/), [Christopher Lord](https://onco.cc/people/chris-lord/), [Eileen M. O'Reilly](https://onco.cc/people/eileen-oreilly/), [Isabelle Ray-Coquard](https://onco.cc/people/isabelle-ray-coquard/), [Jennifer K. Litton](https://onco.cc/people/jennifer-litton/), [Johann de Bono](https://onco.cc/people/johann-de-bono/), [Jonathan A. Ledermann](https://onco.cc/people/jonathan-ledermann/), [Kathleen N. Moore](https://onco.cc/people/kathleen-moore/), [Kim N. Chi](https://onco.cc/people/kim-chi/), [Maha Hussain](https://onco.cc/people/maha-hussain/), [Mansoor Raza Mirza](https://onco.cc/people/mansoor-raza-mirza/), [Neeraj Agarwal](https://onco.cc/people/neeraj-agarwal/), [Robert H. Mach](https://onco.cc/people/robert-mach/), [Robert L. Coleman](https://onco.cc/people/robert-coleman/), [Ruth Plummer](https://onco.cc/people/ruth-plummer/), [Serena Nik-Zainal](https://onco.cc/people/serena-nik-zainal/), [Susan M. Domchek](https://onco.cc/people/susan-domchek/), [Talia Golan](https://onco.cc/people/talia-golan/), [Thomas Helleday](https://onco.cc/people/thomas-helleday/), [Ursula A. Matulonis](https://onco.cc/people/ursula-matulonis/)
- companies: [Clovis Oncology](https://onco.cc/companies/clovis-oncology/), [pharma&](https://onco.cc/companies/pharmaand/)

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JSON: https://onco.cc/api/v1/entities/parp.json