{"entity":{"id":"parp","kind":"target","name":"PARP","aka":["PARP1","PARP1/2 inhibitor class"],"tldr":"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.","summary":"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.","asOf":"2026-10-06","wikipedia":"https://en.wikipedia.org/wiki/PARP_inhibitor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/PARP_inhibitor"},{"label":"TBCRC 048 expansion","url":"https://doi.org/10.1200/JCO-25-02075"},{"label":"TBCRC 048 original cohorts","url":"https://doi.org/10.1200/JCO.20.02151"},{"label":"ClinicalTrials.gov NCT06167317","url":"https://clinicaltrials.gov/study/NCT06167317"},{"label":"ClinicalTrials.gov NCT05417594","url":"https://clinicaltrials.gov/study/NCT05417594"}],"tags":["synthetic-lethality"],"related":[],"cancers":["ovarian","tnbc","breast-hr-positive","prostate","pancreatic","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":["saruparib","palacaparib","eik1004","hrs-1167","nms-03305293","gs-0201","hs-10502","snv1521","dsb2455","imp1734","vb15010","olaparib","niraparib","talazoparib","rucaparib"],"companies":[],"institutions":[],"pathways":["ddr"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-abida-triton2-rucaparib-brca-jco-2020","paper-quigley-brca2-reversion-cfdna-parp-resistance-cancer-discov-2017"],"journals":[],"dependsOn":[],"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)."],"symbol":"PARP1","role":[],"sources":[],"specificity":"broadly-expressed","distribution":"few-types","specificityNote":"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.)","specificitySources":[{"label":"Human Protein Atlas PARP1 tissue","url":"https://www.proteinatlas.org/ENSG00000143799-PARP1/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000143799 associations","url":"https://platform.opentargets.org/target/ENSG00000143799/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:270","ensembl":"ENSG00000143799","uniprot":"P09874","entrez":"142","firstDescribed":1987,"firstDescribedBasis":"sequence","firstDescribedNote":"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\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/3120710/","biology":"Poly(ADP-ribose) polymerase 1 senses single-strand breaks; trapping on DNA is the key cytotoxic mechanism.","whereFound":["BRCA/HRD ovarian, breast, prostate, pancreatic cancers"],"targetClass":"enzyme","prevalence":[{"cancerId":"ovarian","pct":"50","measure":"HRD-positive (BRCA or genomic scar)","source":"https://en.wikipedia.org/wiki/PARP_inhibitor","note":"~20% germline/somatic BRCA"},{"cancerId":"tnbc","pct":"15-20","measure":"Germline BRCA1/2","source":"https://en.wikipedia.org/wiki/PARP_inhibitor","note":"~40-50% HRD by scar"},{"cancerId":"prostate","pct":"20-25","measure":"HRR gene alteration (mCRPC)","source":"https://www.cbioportal.org/study/summary?id=prad_tcga_pan_can_atlas_2018","note":"BRCA2 ~8-10%"},{"cancerId":"pancreatic","pct":"5-8","measure":"Germline BRCA1/2 or PALB2","source":"https://www.cbioportal.org/study/summary?id=paad_tcga_pan_can_atlas_2018"}]},"route":"/targets/parp/","neighbours":{"cancer":[{"id":"tnbc-basal-like-1","kind":"cancer","name":"Basal-like 1 triple-negative breast cancer (BL1)","route":"/cancers/tnbc-basal-like-1/"},{"id":"brca-associated-tnbc","kind":"cancer","name":"BRCA-associated triple-negative breast cancer","route":"/cancers/brca-associated-tnbc/"},{"id":"ewing-sarcoma","kind":"cancer","name":"Ewing sarcoma","route":"/cancers/ewing-sarcoma/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"male-breast-cancer","kind":"cancer","name":"Male breast cancer","route":"/cancers/male-breast-cancer/"},{"id":"prostate-mcrpc","kind":"cancer","name":"Metastatic castration-resistant prostate cancer","route":"/cancers/prostate-mcrpc/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"sclc","kind":"cancer","name":"Small-cell lung cancer","route":"/cancers/sclc/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"},{"id":"uterine-sarcoma","kind":"cancer","name":"Uterine sarcoma","route":"/cancers/uterine-sarcoma/"}],"drug":[{"id":"bracanalysis-cdx","kind":"drug","name":"BRACAnalysis CDx","route":"/drugs/bracanalysis-cdx/"},{"id":"dsb2455","kind":"drug","name":"DSB2455","route":"/drugs/dsb2455/"},{"id":"eik1004","kind":"drug","name":"EIK1004","route":"/drugs/eik1004/"},{"id":"gs-0201","kind":"drug","name":"GS-0201","route":"/drugs/gs-0201/"},{"id":"hrs-1167","kind":"drug","name":"HRS-1167","route":"/drugs/hrs-1167/"},{"id":"hs-10502","kind":"drug","name":"HS-10502","route":"/drugs/hs-10502/"},{"id":"imp1734","kind":"drug","name":"IMP1734","route":"/drugs/imp1734/"},{"id":"iniparib","kind":"drug","name":"Iniparib","route":"/drugs/iniparib/"},{"id":"mychoice-cdx","kind":"drug","name":"myChoice CDx","route":"/drugs/mychoice-cdx/"},{"id":"niraparib","kind":"drug","name":"Niraparib","route":"/drugs/niraparib/"},{"id":"nms-03305293","kind":"drug","name":"NMS-03305293","route":"/drugs/nms-03305293/"},{"id":"olaparib","kind":"drug","name":"Olaparib","route":"/drugs/olaparib/"},{"id":"palacaparib","kind":"drug","name":"Palacaparib","route":"/drugs/palacaparib/"},{"id":"rucaparib","kind":"drug","name":"Rucaparib","route":"/drugs/rucaparib/"},{"id":"saruparib","kind":"drug","name":"Saruparib","route":"/drugs/saruparib/"},{"id":"imp4927","kind":"drug","name":"Senaparib (IMP4297)","route":"/drugs/imp4927/"},{"id":"snv1521","kind":"drug","name":"SNV1521","route":"/drugs/snv1521/"},{"id":"talazoparib","kind":"drug","name":"Talazoparib","route":"/drugs/talazoparib/"},{"id":"vb15010","kind":"drug","name":"VB15010","route":"/drugs/vb15010/"},{"id":"veliparib","kind":"drug","name":"Veliparib","route":"/drugs/veliparib/"}],"pathway":[{"id":"ar-signaling","kind":"pathway","name":"Androgen 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