{"entity":{"id":"parp","kind":"target","name":"PARP","aka":["PARP1/2","Poly [ADP-ribose] polymerase 2"],"tldr":"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.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/PARP_inhibitor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/PARP_inhibitor"}],"tags":["synthetic-lethality"],"related":[],"cancers":["ovarian","tnbc","breast-hr-positive","prostate","pancreatic","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":["saruparib","palacaparib"],"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":"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":"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":"talazoparib","kind":"drug","name":"Talazoparib","route":"/drugs/talazoparib/"},{"id":"veliparib","kind":"drug","name":"Veliparib","route":"/drugs/veliparib/"}],"pathway":[{"id":"ar-signaling","kind":"pathway","name":"Androgen receptor signalling","route":"/pathways/ar-signaling/"},{"id":"base-excision-repair-parp","kind":"pathway","name":"Base excision repair, PARP & alkylation damage","route":"/pathways/base-excision-repair-parp/"},{"id":"cgas-sting","kind":"pathway","name":"cGAS-STING innate sensing","route":"/pathways/cgas-sting/"},{"id":"clonal-haematopoiesis","kind":"pathway","name":"Clonal haematopoiesis (CHIP)","route":"/pathways/clonal-haematopoiesis/"},{"id":"ddr","kind":"pathway","name":"DNA damage response & homologous recombination","route":"/pathways/ddr/"},{"id":"replication-stress","kind":"pathway","name":"DNA replication stress","route":"/pathways/replication-stress/"},{"id":"homologous-recombination-repair","kind":"pathway","name":"Double-strand break repair: HR versus end joining","route":"/pathways/homologous-recombination-repair/"},{"id":"mutagenesis-signatures","kind":"pathway","name":"Mutagenesis & mutational signatures","route":"/pathways/mutagenesis-signatures/"},{"id":"pancreatic-cancer-signalling","kind":"pathway","name":"Pancreatic cancer (KEGG map)","route":"/pathways/pancreatic-cancer-signalling/"},{"id":"synthetic-lethality-map","kind":"pathway","name":"Synthetic lethality: paired dependencies","route":"/pathways/synthetic-lethality-map/"}],"paper":[{"id":"paper-quigley-brca2-reversion-cfdna-parp-resistance-cancer-discov-2017","kind":"paper","name":"Analysis of circulating cell-free DNA identifies multiclonal heterogeneity of BRCA2 reversion mutations associated with resistance to PARP inhibitors","route":"/key-papers/paper-quigley-brca2-reversion-cfdna-parp-resistance-cancer-discov-2017/"},{"id":"paper-olympia-nejm-2021","kind":"paper","name":"OlympiA: a year of olaparib after surgery for BRCA-mutated, high-risk early breast cancer","route":"/key-papers/paper-olympia-nejm-2021/"},{"id":"paper-paola-1-nejm-2019","kind":"paper","name":"PAOLA-1: olaparib added to bevacizumab maintenance in newly diagnosed ovarian cancer, with benefit confined to HRD-positive tumours","route":"/key-papers/paper-paola-1-nejm-2019/"},{"id":"paper-profound-nejm-2020","kind":"paper","name":"PROfound: olaparib for metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations","route":"/key-papers/paper-profound-nejm-2020/"},{"id":"paper-solo-1-nejm-2018","kind":"paper","name":"SOLO-1: two years of olaparib maintenance after first-line chemotherapy for BRCA-mutated ovarian cancer","route":"/key-papers/paper-solo-1-nejm-2018/"},{"id":"paper-abida-triton2-rucaparib-brca-jco-2020","kind":"paper","name":"TRITON2: rucaparib in men with metastatic castration-resistant prostate cancer harbouring a BRCA1 or BRCA2 alteration","route":"/key-papers/paper-abida-triton2-rucaparib-brca-jco-2020/"}],"trial":[{"id":"athena-mono","kind":"trial","name":"ATHENA-MONO / GOG-3020","route":"/trials/athena-mono/"},{"id":"brocade3","kind":"trial","name":"BROCADE3","route":"/trials/brocade3/"},{"id":"duo-e","kind":"trial","name":"DUO-E / GOG-3041 / ENGOT-EN10","route":"/trials/duo-e/"},{"id":"duo-o","kind":"trial","name":"DUO-O / ENGOT-ov46","route":"/trials/duo-o/"},{"id":"embraca","kind":"trial","name":"EMBRACA","route":"/trials/embraca/"},{"id":"olympiad","kind":"trial","name":"OlympiAD","route":"/trials/olympiad/"},{"id":"paola-1","kind":"trial","name":"PAOLA-1 / ENGOT-ov25","route":"/trials/paola-1/"},{"id":"phoenix","kind":"trial","name":"PHOENIX DDR/Anti-PD-L1","route":"/trials/phoenix/"},{"id":"polo","kind":"trial","name":"POLO","route":"/trials/polo/"},{"id":"prima","kind":"trial","name":"PRIMA / ENGOT-OV26","route":"/trials/prima/"},{"id":"profound","kind":"trial","name":"PROfound","route":"/trials/profound/"},{"id":"solo-1","kind":"trial","name":"SOLO-1","route":"/trials/solo-1/"},{"id":"talapro-2","kind":"trial","name":"TALAPRO-2","route":"/trials/talapro-2/"},{"id":"triton3","kind":"trial","name":"TRITON3","route":"/trials/triton3/"}],"idea":[{"id":"idea-tr2-hrd-functional-standard","kind":"idea","name":"A functional test for homologous recombination deficiency validated across laboratories","route":"/ideas/idea-tr2-hrd-functional-standard/"},{"id":"idea-moon-synthetic-lethality-map-every-driver","kind":"idea","name":"A synthetic lethality map for every cancer driver in every tissue context","route":"/ideas/idea-moon-synthetic-lethality-map-every-driver/"},{"id":"idea-sclc-subtype-directed","kind":"idea","name":"Subtype-directed therapy for SCLC (ASCL1 / NEUROD1 / POU2F3 / inflamed)","route":"/ideas/idea-sclc-subtype-directed/"},{"id":"idea-chip-risk-modifiers","kind":"idea","name":"Which patients' blood clones will become leukaemia after treatment?","route":"/ideas/idea-chip-risk-modifiers/"}],"pairing":[{"id":"parp-plus-bevacizumab","kind":"pairing","name":"PARP inhibitor + bevacizumab maintenance (HRD-positive)","route":"/pairings/parp-plus-bevacizumab/"}],"term":[{"id":"brca-reversion-mutations","kind":"term","name":"BRCA reversion mutations","route":"/terms/brca-reversion-mutations/"},{"id":"checkpoint","kind":"term","name":"Checkpoint (two meanings)","route":"/terms/checkpoint/"},{"id":"genome-instability-mutation","kind":"term","name":"Enabling characteristic: genome instability and mutation","route":"/terms/genome-instability-mutation/"},{"id":"enzyme","kind":"term","name":"Enzyme","route":"/terms/enzyme/"},{"id":"hrd","kind":"term","name":"Homologous recombination deficiency (HRD)","route":"/terms/hrd/"},{"id":"hrd-in-breast-cancer","kind":"term","name":"Homologous recombination deficiency (HRD) in breast cancer","route":"/terms/hrd-in-breast-cancer/"},{"id":"sclc-molecular-subtypes","kind":"term","name":"Small-cell lung cancer transcription-factor subtypes (SCLC-A, SCLC-N, SCLC-P, SCLC-I) and SLFN11","route":"/terms/sclc-molecular-subtypes/"},{"id":"tumour-suppressor-gene","kind":"term","name":"Tumour suppressor gene","route":"/terms/tumour-suppressor-gene/"},{"id":"prostate-hrr-eligibility","kind":"term","name":"Who is eligible for a PARP inhibitor in prostate cancer, and why the gene matters","route":"/terms/prostate-hrr-eligibility/"}],"roadmap":[{"id":"pancreatic-roadmap","kind":"roadmap","name":"Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question","route":"/roadmaps/pancreatic-roadmap/"}],"biomarker":[{"id":"hrr-gene-mutation","kind":"biomarker","name":"Homologous recombination repair gene mutation in prostate cancer","route":"/biomarkers/hrr-gene-mutation/"}],"technology":[{"id":"hrd-testing","kind":"technology","name":"HRD & BRCA testing","route":"/technologies/hrd-testing/"},{"id":"hrd-genomic-scar-scores","kind":"technology","name":"HRD genomic scar scores (GIS, LOH, HRDetect)","route":"/technologies/hrd-genomic-scar-scores/"},{"id":"parp-inhibitor","kind":"technology","name":"PARP inhibitors","route":"/technologies/parp-inhibitor/"},{"id":"parp-pet","kind":"technology","name":"PARP PET","route":"/technologies/parp-pet/"},{"id":"rad51-foci-assay","kind":"technology","name":"RAD51 foci assay (functional HRD test)","route":"/technologies/rad51-foci-assay/"},{"id":"radionuclide-parp-combination","kind":"technology","name":"Radioligand plus DNA-repair inhibitor combinations","route":"/technologies/radionuclide-parp-combination/"},{"id":"synthetic-lethality-approaches","kind":"technology","name":"Synthetic lethality approaches","route":"/technologies/synthetic-lethality-approaches/"}],"institution":[{"id":"penn-abramson","kind":"institution","name":"Abramson Cancer Center, University of Pennsylvania","route":"/institutions/penn-abramson/"},{"id":"newcastle-cancer-centre","kind":"institution","name":"Newcastle Cancer Centre / Northern Centre for Cancer Care","route":"/institutions/newcastle-cancer-centre/"},{"id":"sheba","kind":"institution","name":"Sheba Medical Center","route":"/institutions/sheba/"},{"id":"stephenson-oklahoma","kind":"institution","name":"Stephenson Cancer Center, OU Health","route":"/institutions/stephenson-oklahoma/"}],"person":[{"id":"alan-ashworth","kind":"person","name":"Alan Ashworth","route":"/people/alan-ashworth/"},{"id":"alan-dandrea","kind":"person","name":"Alan D. D'Andrea","route":"/people/alan-dandrea/"},{"id":"amit-oza","kind":"person","name":"Amit M. Oza","route":"/people/amit-oza/"},{"id":"andrew-tutt","kind":"person","name":"Andrew Tutt","route":"/people/andrew-tutt/"},{"id":"charles-geyer","kind":"person","name":"Charles E. Geyer Jr.","route":"/people/charles-geyer/"},{"id":"chris-lord","kind":"person","name":"Christopher Lord","route":"/people/chris-lord/"},{"id":"eileen-oreilly","kind":"person","name":"Eileen M. O'Reilly","route":"/people/eileen-oreilly/"},{"id":"isabelle-ray-coquard","kind":"person","name":"Isabelle Ray-Coquard","route":"/people/isabelle-ray-coquard/"},{"id":"jennifer-litton","kind":"person","name":"Jennifer K. Litton","route":"/people/jennifer-litton/"},{"id":"johann-de-bono","kind":"person","name":"Johann de Bono","route":"/people/johann-de-bono/"},{"id":"jonathan-ledermann","kind":"person","name":"Jonathan A. Ledermann","route":"/people/jonathan-ledermann/"},{"id":"kathleen-moore","kind":"person","name":"Kathleen N. Moore","route":"/people/kathleen-moore/"},{"id":"kim-chi","kind":"person","name":"Kim N. Chi","route":"/people/kim-chi/"},{"id":"maha-hussain","kind":"person","name":"Maha Hussain","route":"/people/maha-hussain/"},{"id":"mansoor-raza-mirza","kind":"person","name":"Mansoor Raza Mirza","route":"/people/mansoor-raza-mirza/"},{"id":"neeraj-agarwal","kind":"person","name":"Neeraj Agarwal","route":"/people/neeraj-agarwal/"},{"id":"robert-mach","kind":"person","name":"Robert H. Mach","route":"/people/robert-mach/"},{"id":"robert-coleman","kind":"person","name":"Robert L. Coleman","route":"/people/robert-coleman/"},{"id":"ruth-plummer","kind":"person","name":"Ruth Plummer","route":"/people/ruth-plummer/"},{"id":"serena-nik-zainal","kind":"person","name":"Serena Nik-Zainal","route":"/people/serena-nik-zainal/"},{"id":"susan-domchek","kind":"person","name":"Susan M. Domchek","route":"/people/susan-domchek/"},{"id":"talia-golan","kind":"person","name":"Talia Golan","route":"/people/talia-golan/"},{"id":"thomas-helleday","kind":"person","name":"Thomas Helleday","route":"/people/thomas-helleday/"},{"id":"ursula-matulonis","kind":"person","name":"Ursula A. Matulonis","route":"/people/ursula-matulonis/"}],"company":[{"id":"clovis-oncology","kind":"company","name":"Clovis Oncology","route":"/companies/clovis-oncology/"},{"id":"pharmaand","kind":"company","name":"pharma&","route":"/companies/pharmaand/"}]}}