Loading
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.
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.
In plain words · 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.
Backbone ribbon from PDB 7KK4. RCSB PDB 7KK4. The ribbon widens where the chain is folded into a regular pattern and narrows where it is a loose loop.
Backbone ribbon with the bound drug in ball-and-stick (pink carbons). The wireframe view adds the pocket residues within 5 Å as a thin cage.
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.
Poly(ADP-ribose) polymerase 1 senses single-strand breaks; trapping on DNA is the key cytotoxic mechanism.
11 products aim at PARP: small molecules and other agents. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
Broadly expressed or essential: HPA finds the RNA at low tissue specificity; the 9 medicines aimed at it (Saruparib, Palacaparib, BRACAnalysis CDx and more) act on the wild-type protein, so normal tissue is exposed and the therapeutic window comes from the tumour's faster division or its dependence on the protein. HPA PARP1: RNA low tissue specificity; high antibody staining in 16 normal tissues; highest cancer staining glioma (12 of 12 high). Distribution: 4 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Ovarian cancer, Breast cancer (all types), Prostate cancer, Pancreatic ductal adenocarcinoma); Open Targets associates it with 7 specific cancer types at or above 0.5 (ovarian cancer, breast cancer, ovarian carcinoma, fallopian tube cancer, prostate cancer, primary peritoneal carcinoma and more). (Rule 7 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas PARP1 tissue; Open Targets ENSG00000143799 associations
First described 1987. Earliest sequence paper UniProt cites for the protein: Uchida et al, Biochem. Biophys. Res. Commun, 1987, "Nucleotide sequence of a full-length cDNA for human fibroblast poly(ADP-ribose) polymerase". Source.
Poly(ADP-ribose) polymerase 1 senses single-strand breaks; trapping on DNA is the key cytotoxic mechanism.
RNA: low tissue specificity, detected in all normal tissues.
Medium: Adipose tissue, Adrenal gland, Appendix, Cervix, Duodenum, Endometrium, Epididymis, Esophagus.
HPA PARP1 tissue · HPA PARP1 pathology · HPA protein class: FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Ovarian cancer | 50% | HRD-positive (BRCA or genomic scar) | ~20% germline/somatic BRCA | Wikipedia |
| Prostate cancer | 20-25% | HRR gene alteration (mCRPC) | BRCA2 ~8-10% | cBioPortal (TCGA) |
| Triple-negative breast cancer | 15-20% | Germline BRCA1/2 | ~40-50% HRD by scar | Wikipedia |
| Pancreatic ductal adenocarcinoma | 5-8% | Germline BRCA1/2 or PALB2 | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
The inherited BRCA test that decides who can have PARP inhibitor pills for ovarian, breast, pancreatic and prostate cancer.
Billed as the first PARP inhibitor for triple-negative breast cancer, it failed its phase 3 in 2011. It turned out not to inhibit PARP at all.
A tumour test that measures DNA-repair scarring so that women with ovarian cancer beyond BRCA carriers can benefit from PARP inhibitors.
Niraparib is a PARP inhibitor approved as maintenance for ovarian cancer regardless of BRCA status, and in prostate cancer with abiraterone.
Olaparib was the first PARP inhibitor, and turned an inherited BRCA mutation from a risk factor into a drug target, including after surgery in breast cancer.
Palacaparib is an experimental small-molecule drug from AstraZeneca in phase 2 trials for ovarian cancer, non-small-cell lung cancer and endometrial cancer, aimed at PARP.
A PARP inhibitor for BRCA-mutated ovarian and prostate cancer whose original maker went bankrupt; still available, with a narrowed label.
Saruparib is an experimental small-molecule drug from AstraZeneca in phase 3 trials for prostate cancer, ovarian cancer and non-small-cell lung cancer, aimed at PARP.
Senaparib is an oral PARP inhibitor from IMPACT Therapeutics tested as maintenance treatment after first-line chemotherapy for advanced ovarian cancer. On 17 September 2026 the EMA's medicines committee recommended EU approval under the name Sepalna; the European Commission's decision is pending.
Talazoparib is a PARP inhibitor that traps PARP on DNA about 100 times more strongly than olaparib, which is why it works at a 1 mg daily dose. It is approved for germline BRCA-mutant HER2-negative breast cancer and, with enzalutamide, for HRR-mutant castration-resistant prostate cancer; anaemia is its dominant side effect.
Veliparib is a PARP inhibitor that AbbVie tested with chemotherapy in breast cancer. It added nothing to carboplatin before surgery (BrighTNess) and lengthened progression-free but not overall survival with carboplatin and paclitaxel in inherited BRCA advanced disease (BROCADE3), so it was never licensed.
Everyone with HER2-negative early breast cancer that meets high-risk criteria should be offered germline BRCA testing, because a positive result now changes treatment: a year of olaparib after chemotherapy reduces relapse and death. It does not apply to low-risk tumours, HER2-positive disease, or somatic-only BRCA mutations.
Germline and tumour testing for homologous recombination repair genes is now standard in metastatic prostate cancer, and olaparib is approved for BRCA-mutated disease after a hormonal agent.
The trial behind the second PARP inhibitor licensed in prostate cancer, and the evidence that a somatic BRCA alteration predicts response as well as an inherited one. Together with TOPARP-A it is why tumour as well as germline sequencing is recommended in metastatic disease.
Women with newly diagnosed advanced ovarian cancer should have their tumour tested for BRCA mutations and homologous recombination deficiency, because those who are HRD-positive gain years of additional disease control and better survival from adding olaparib to bevacizumab maintenance. Those who are HRD-negative gain nothing from olaparib in this combination and should not be exposed to its toxicity and cost. HRD testing has become a routine part of ovarian cancer care as a result.
Every woman diagnosed with advanced high-grade ovarian cancer should be tested for BRCA mutations at diagnosis, because those who carry one should receive two years of olaparib after chemotherapy, which greatly extends the time in remission and improves long-term survival. The plateau in the survival curves suggests some patients are cured by this approach. Toxicity is mostly anaemia, fatigue and nausea, and the two-year limit appears sufficient.
It establishes that PARP inhibitor resistance in prostate cancer is a restored repair pathway rather than a bypass, which is why platinum and PARP inhibitors lose activity together, and it is the argument for sampling plasma rather than one lesion at progression.
Query for this target: (TITLE:"PARP" OR ABSTRACT:"PARP" OR TITLE:"PARP1" OR ABSTRACT:"PARP1" OR TITLE:"PARP1/2" OR ABSTRACT:"PARP1/2" OR TITLE:"Poly [ADP-ribose] polymerase 2" OR ABSTRACT:"Poly [ADP-ribose] polymerase 2") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about PARP, not a curated reading list.
Shares Christopher Lord, Jonathan A. Ledermann, Thomas Helleday, Alan D. D'Andrea.
Shares Christopher Lord, A synthetic lethality map for every cancer driver in every tissue context, Tumour suppressor gene, SOLO-1: two years of olaparib maintenance after first-line chemotherapy for BRCA-mutated ovarian cancer.
Shares ATHENA-MONO / GOG-3020, PARP inhibitor + bevacizumab maintenance (HRD-positive), DUO-O / ENGOT-ov46, SOLO-1.
Shares Alan D. D'Andrea, Radioligand plus DNA-repair inhibitor combinations, Subtype-directed therapy for SCLC (ASCL1 / NEUROD1 / POU2F3 / inflamed), Enabling characteristic: genome instability and mutation.
Shares Analysis of circulating cell-free DNA identifies multiclonal heterogeneity of BRCA2 reversion mutations associated with resistance to PARP inhibitors, myChoice CDx, BRCA reversion mutations, TRITON2: rucaparib in men with metastatic castration-resistant prostate cancer harbouring a BRCA1 or BRCA2 alteration.
Shares Susan M. Domchek, Talia Golan, POLO, BRCA reversion mutations.
Shares BROCADE3, BRACAnalysis CDx, PROfound: olaparib for metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations, BRCA reversion mutations.
Shares SOLO-1, PRIMA / ENGOT-OV26, PAOLA-1 / ENGOT-ov25, BRCA reversion mutations.