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PARP inhibitors block DNA repair. Some cancers with defective repair are especially vulnerable, but the gene, disease setting and treatment combination determine which evidence applies.
PARP1 and PARP2 are distinct DNA-repair enzymes. This page covers drugs that inhibit one or both; the molecular structures and identifiers shown here refer to PARP1. Approved PARP1/2 inhibitors exploit repair dependency, while selective PARP1 programmes seek a wider therapeutic window. Biomarker selection varies by country, drug and disease: US breast labels for olaparib and talazoparib require germline BRCA alterations; somatic BRCA breast activity is supported by metastatic phase 2 evidence rather than an adjuvant approval. Genomic HRD scars, current functional repair and individual HRR genes are not interchangeable. In TBCRC 048, ATM or CHEK2 alterations alone did not produce responses; the 2026 expansion found activity in germline PALB2 and somatic BRCA cohorts, but the somatic cohort missed its prespecified response target. PARP inhibitors can cause substantial marrow toxicity. GS-0201 plus sacituzumab govitecan and palacaparib plus datopotamab deruxtecan connect repair dependency with antibody-directed delivery in early trials.
In plain words · PARP inhibitors block DNA repair. Some cancers with defective repair are especially vulnerable, but the gene, disease setting and treatment combination determine which evidence applies.
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 inhibitors block DNA repair. Some cancers with defective repair are especially vulnerable, but the gene, disease setting and treatment combination determine which evidence applies.
Poly(ADP-ribose) polymerase 1 senses single-strand breaks; trapping on DNA is the key cytotoxic mechanism.
20 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.
DSB2455 is an experimental pill being studied to block a DNA-repair enzyme in cancer cells.
EIK1004 is an experimental pill being studied to block a DNA-repair enzyme in cancer cells.
GS-0201 is an experimental pill being studied to block a DNA-repair enzyme in cancer cells.
HRS-1167 is an experimental pill being studied to block a DNA-repair enzyme in cancer cells.
HS-10502 is an experimental pill being studied to block a DNA-repair enzyme in cancer cells.
EIK1003, formerly IMP1734, is an experimental pill that blocks the PARP1 DNA-repair enzyme.
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 DNA-repair inhibitor used after chemotherapy for selected ovarian cancers and with hormone treatment for selected BRCA-mutated prostate cancers.
NMS-03305293 is an experimental pill being studied to block a DNA-repair enzyme in cancer cells.
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 DNA-repair inhibitor designed to reach the brain and selectively block PARP1.
Rucaparib is a DNA-repair inhibitor for selected BRCA-mutated ovarian and prostate cancers. Its prostate indication received regular US approval in December 2025.
Saruparib is an experimental DNA-repair inhibitor in advanced trials for selected breast and prostate cancers. It selectively blocks PARP1.
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.
SNV1521 is an experimental pill being studied to block a DNA-repair enzyme in cancer cells.
Talazoparib is a DNA-repair inhibitor for selected inherited-BRCA breast cancers and, with hormone treatment, selected advanced prostate cancers.
VB15010 is an experimental pill targeting the PARP1 DNA-repair enzyme.
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.
Observational prescribing/safety data do not establish efficacy, comparative benefit or safety after prior pneumonitis.
Metastatic single-arm evidence does not supply a somatic-only adjuvant indication or a personal response probability.
Mixed, heavily pretreated cancers and no control arm; cannot compare its ORR directly with olaparib trials or establish postoperative benefit.
Negative result for the tested low-exposure combination; not proof that every rucaparib or PARP strategy fails.
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.
Query for this target: (TITLE:"PARP" OR ABSTRACT:"PARP" OR TITLE:"PARP1" OR ABSTRACT:"PARP1" OR TITLE:"PARP1/2 inhibitor class" OR ABSTRACT:"PARP1/2 inhibitor class") 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 Efficacy and Safety Comparison of Niraparib to Placebo in Participants With Human Epidermal Growth Factor 2 Negative (HER2-) Breast Cancer Susceptibility Gene Mutation (BRCAmut) or Triple-Negative Breast Cancer (TNBC) With Molecular Disease, BROCADE3, BRACAnalysis CDx, PARTNER.
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 Susan M. Domchek, Talia Golan, POLO, BRCA reversion mutations.
Shares Study of AZD0516 as Monotherapy and in Combination in Participants With Metastatic Prostate Cancer, Study of AZD4956 as Monotherapy and in Combination With Anti-Cancer Agents in Participants With Advanced/Metastatic Homologous Recombination Deficient Solid Tumours, A Study of Metastases Free Survival With Saruparib vs Placebo Added to a Standard RT/ADT in Men With High-risk Prostate Cancer With a BRCA Mutation, A Trial to Learn How Safe AZD9750 is and How Well it Works in People With Metastatic Prostate Cancer When Given With or Without Other Anticancer Drugs.
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.
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