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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. This dossier gathers the 11 products (6 approved), 97 trials, 4 pathways and 9 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
Poly(ADP-ribose) polymerase 1 senses single-strand breaks; trapping on DNA is the key cytotoxic mechanism.
| 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.
| Modality | Approved | Phase 3 | Phase 2 | Withdrawn or failed |
|---|---|---|---|---|
| Small molecule 9 | ||||
| Test or device 2 | - | - | - |
| Trial | Setting | Result | Products | ||
|---|---|---|---|---|---|
| 3 | Active | A Phase 3 Randomized, Placebo-controlled, Double-blind Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for the Treatment of Participants With Deleterious Germline or Somatic Homologous Recombination Repair (HRR) Gene-Mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC) | - | ||
| 3 | Active | A Randomized, Double-blind, Phase 3 Comparison of Platinum-based Therapy With TSR-042 and Niraparib Versus Standard of Care Platinum-based Therapy as First-line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer | - | ||
| 3 | Active | A Randomized Phase 3 Double-Blinded Study Comparing the Efficacy and Safety of Niraparib to Placebo in Participants With Either HER2-Negative BRCA-Mutated or Triple-Negative Breast Cancer With Molecular Disease Based on Presence of Circulating Tumor DNA After Definitive Therapy (ZEST) | - | ||
| 3 | Active | A Randomised, Double-blind, Placebo-controlled, Multicentre Phase III Study of Olaparib Plus Abiraterone Relative to Placebo Plus Abiraterone as First-line Therapy in Men With Metastatic Castration-resistant Prostate Cancer (PROpel Study) | - | ||
DUO-E / GOG-3041 / ENGOT-EN10 NCT04269200 | 3 | Positive | Newly diagnosed advanced or recurrent endometrial cancer: chemotherapy + durvalumab, then durvalumab ± olaparib maintenance, vs chemotherapy | PFS HR 0.42 (dMMR, durvalumab); 0.57 (pMMR, durvalumab + olaparib). | |
DUO-O / ENGOT-ov46 NCT03737643 | 3 | Mixed | Newly diagnosed non-BRCA-mutated advanced ovarian cancer: chemotherapy + bevacizumab + durvalumab, then durvalumab + bevacizumab ± olaparib maintenance, vs standard | PFS HR 0.63; interim OS HR 0.95. | |
TALAPRO-2 NCT03395197 | 3 | Positive | First-line mCRPC: enzalutamide + talazoparib vs enzalutamide + placebo (all-comers and HRR-mutant cohorts) | rPFS HR 0.63 (ITT); OS HR 0.80 (ITT), 0.62 (HRR-mutant). | |
TRITON3 NCT02975934 | 3 | Mixed | Metastatic castration-resistant prostate cancer with a BRCA1, BRCA2 or ATM alteration and progression after a second-generation androgen receptor pathway inhibitor: rucaparib 600 mg twice daily against physician's choice of docetaxel or a second androgen receptor pathway inhibitor, randomised 2:1, with imaging-based progression-free survival by independent review as the primary outcome | Median imaging-based progression-free survival 11.2 against 6.4 months in the BRCA subgroup (hazard ratio 0.50, 95 percent confidence interval 0.36 to 0.69) and 10.2 against 6.4 months overall (0.61, 0.47 to 0.80); no effect in the ATM subgroup (0.95, 0.59 to 1.52). | |
ATHENA-MONO / GOG-3020 NCT03522246 | 3 | Positive | Newly diagnosed advanced ovarian cancer after response to first-line platinum: rucaparib maintenance vs placebo | PFS 20.2 vs 9.2 months (HR 0.52). | |
MAGNITUDE NCT03748641 | 3 | Mixed | First-line mCRPC: abiraterone + niraparib vs abiraterone + placebo, HRR-mutant and HRR-negative cohorts | BRCA cohort rPFS HR 0.53; HRR-negative futility. | |
PROpel NCT03732820 | 3 | Positive | First-line mCRPC, all-comers: abiraterone + olaparib vs abiraterone + placebo | rPFS HR 0.66 (ITT); OS HR 0.81 (NS). | |
OlympiA NCT02032823 | 3 | Positive | Adjuvant olaparib for one year in germline BRCA-mutated, HER2-negative, high-risk early breast cancer | iDFS HR 0.58; OS HR 0.72. | |
BROCADE3 NCT02163694 | 3 | Mixed | Germline BRCA1 or BRCA2-mutated HER2-negative metastatic or locally advanced unresectable breast cancer, up to two prior chemotherapy lines: carboplatin and paclitaxel with veliparib or placebo, continued as veliparib monotherapy if chemotherapy stopped, 147 hospitals in 36 countries | PFS 14.5 vs 12.6 months (HR 0.71, p 0.0016); final OS 32.4 vs 28.2 months (HR 0.92, p 0.43). Not licensed. | |
PROfound NCT02987543 | 3 | Positive | mCRPC with HRR gene alterations after ARPI: olaparib vs enzalutamide/abiraterone switch | rPFS HR 0.34; OS HR 0.69 (cohort A). | |
PAOLA-1 / ENGOT-ov25 NCT02477644 | 3 | Positive | Newly diagnosed advanced ovarian cancer already on bevacizumab maintenance: adding olaparib vs placebo | PFS HR 0.59 overall, 0.33 HRD-positive; 5-year OS 65.5% vs 48.4% in HRD-positive. | |
POLO NCT02184195 | 3 | Mixed | Germline BRCA-mutated metastatic PDAC not progressed on ≥16 weeks of platinum: olaparib maintenance vs placebo | PFS HR 0.53; OS HR 0.83 (not significant). | |
PRIMA / ENGOT-OV26 NCT02655016 | 3 | Mixed | Newly diagnosed advanced ovarian cancer at high risk of relapse, any BRCA/HRD status: niraparib maintenance vs placebo | PFS HR 0.62 overall, 0.43 HRD-positive; final OS HR 1.01. | |
BrighTNess NCT02032277 | 3 | Completed | Stage II to III triple-negative breast cancer before surgery: paclitaxel with carboplatin and the PARP inhibitor veliparib, paclitaxel with carboplatin and placebo, or paclitaxel alone, each followed by doxorubicin and cyclophosphamide | Carboplatin added to neoadjuvant paclitaxel raised the pathological complete response rate and improved event-free survival in triple-negative breast cancer; veliparib added nothing to carboplatin. | |
EMBRACA NCT01945775 | 3 | Positive | Germline BRCA-mutated, HER2-negative locally advanced or metastatic breast cancer: talazoparib vs physician's choice chemotherapy | PFS 8.6 vs 5.6 months, HR 0.54; OS HR 0.85, not significant. | |
| 3 | Active | Phase III Randomised, Double Blind, Placebo Controlled Study of Olaparib Maintenance Monotherapy in Platinum Sensitive Relapsed BRCA Mutated Ovarian Cancer Patients With a Complete or Partial Response Following Platinum Based Chemotherapy | - | ||
SOLO-1 NCT01844986 | 3 | Positive | Newly diagnosed advanced BRCA-mutated ovarian cancer in response to platinum chemotherapy: olaparib maintenance for 2 years vs placebo | PFS HR 0.30; 7-year OS 67.0% vs 46.5% (HR 0.55). | |
OlympiAD NCT02000622 | 3 | Positive | Germline BRCA-mutated, HER2-negative metastatic breast cancer after up to two chemotherapy lines: olaparib vs physician's choice chemotherapy | PFS 7.0 vs 4.2 months, HR 0.58; OS 19.3 vs 17.1 months, not significant. | |
| 3 | Completed | A Phase 3, Multi-Center, Open-Label, Randomized Study of Gemcitabine/Carboplatin, With or Without BSI-201, in Patients With ER-, PR-, and Her2-Negative Metastatic Breast Cancer | - | ||
| 3 | Active | A Phase III Study to Evaluate the Efficacy and Safety of IMP4297 Following 1st Line Chemotherapy in the Monotherapy Maintenance Treatment of Subjects With Ovarian Cancer | - | ||
| 3 | Recruiting | A Randomised, Double-blind, Placebo-controlled, Phase III Study of Adjuvant Saruparib (AZD5305) in Patients With BRCAm Localised High-Risk Prostate Cancer Receiving Radiotherapy With Androgen Deprivation Therapy (EvoPAR-Prostate02) | - | ||
| 3 | Active | AVELUMAB MASTER PROTOCOL: AN OPEN-LABEL CONTINUATION STUDY FOR PARTICIPANTS CONTINUING FROM PFIZER-SPONSORED AVELUMAB CLINICAL STUDIES. | - | ||
D9319C00001- 1L OC Mono Global RCT NCT04884360 | 3 | Active | A Randomised, Double-blind, Placebo-controlled, Phase III Study of Olaparib Maintenance Monotherapy in Participants With BRCA Wild Type Advanced High Grade Serous or Endometrioid Ovarian Cancer Following Response to Standard First-line Platinum-based Chemotherapy (MONO-OLA1) | - | |
| 3 | Completed | Molecular Profiling of Advanced Soft-tissue Sarcomas. A Phase III Study | - | ||
| 3 | Planned | PembroLizumab Adjuvant in Patients With Early-stage Triple NEgaTive Breast Cancer With Residual Disease After Neoadjuvant Pembrolizumab Plus Chemotherapy - the Multicenter, Randomized Phase III, Pragmatic PLANET Trial | - | ||
| 3 | Recruiting | A Randomized Phase 3 Trial Evaluating the Safety & Efficacy of IP IMNN-001 Administered in Combination w/ Standard Neoadjuvant & Adjuvant Chemotherapy in Newly Diagnosed Patients w/ Advanced EOC, Fallopian Tube or Primary Peritoneal Cancer | - |
Secondary mutations restore the open reading frame and homologous recombination; also confers platinum resistance.
Loss of end-protection factors lets BRCA1-deficient cells resect DNA ends and repair by HR.
Stabilised forks tolerate PARP trapping; PARP1 mutations abolish trapping.
Olaparib and rucaparib are P-gp substrates.
More receptor, or mutations (F877L, T878A) that turn antagonists into agonists.
Truncated receptor lacking the ligand-binding domain is constitutively active and invisible to enzalutamide.
RB1/TP53 loss enables transdifferentiation; AR-indifferent, DLL3-positive, PSMA-negative.
Reciprocal feedback between AR and PI3K pathways.
GR drives an AR-like transcriptional programme under enzalutamide.
Tens of thousands of times a day a single DNA letter is oxidised or chemically scarred. A small crew snips it out and PARP marks the nick so it gets sealed. PARP inhibitors do not just switch PARP off; they trap it on the DNA, turning a harmless nick into a lethal break when the cell copies its DNA.
Which nodes have drugs →The DNA damage response is the cell's set of repair crews. Single-strand breaks are patched by PARP; double-strand breaks by BRCA-dependent homologous recombination. Lose one crew and the cell survives; lose both and it dies. That is how PARP inhibitors work.
Which nodes have drugs →A break through both strands of DNA is the most dangerous lesion a cell faces. Two crews compete to fix it: homologous recombination copies the answer from the sister chromosome (accurate, needs BRCA), while end joining simply glues the ends (fast, sloppy). Which crew wins decides whether PARP inhibitors and radiation kill the cell.
Which nodes have drugs →Two genes are synthetically lethal when losing either alone is fine but losing both kills the cell. Cancers that have already lost one (a tumour suppressor you cannot put back) become uniquely dependent on the other, which you can drug. BRCA and PARP was the first proof; a dozen more pairs are now in trials.
Which nodes have drugs →| Assay | Platform | Cut-off | Gates |
|---|---|---|---|
| FoundationOne CDx Foundation Medicine (Roche) · FDA CDx 2017 | NGS tissue | Per companion claim: EGFR, ALK, BRAF V600, ERBB2 amplification, KRAS wild-type, BRCA1/2 and HRR genes, PIK3CA, MET exon 14, RET, FGFR2 fusions, IDH1, NTRK fusions; MSI-high; TMB at least 10 mutations per megabase | |
| BRACAnalysis CDx Myriad Genetics · FDA CDx 2014 | Germline NGS | Deleterious or suspected deleterious germline variant | |
| myChoice CDx Myriad Genetics · FDA CDx 2019 | NGS tissue | Genomic instability score at least 42, or BRCA1/2 mutation, defines HRD-positive (olaparib plus bevacizumab, PAOLA-1; niraparib) | |
| FoundationFocus CDxBRCA Foundation Medicine · FDA CDx 2016 | NGS tissue | Deleterious BRCA1/2 alteration (rucaparib, ovarian cancer) |
No model entry for this target yet; check the cancer entries on the models page.
No open questions recorded for this target yet. Suggest one.
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.
The dossier as machine-readable JSON, at /api/v1/dossiers/parp.json: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/parp.json. Licence CC BY-NC 4.0.