{"id":"tp53","name":"TP53","symbol":"TP53","route":"/targets/tp53/","asOf":"2026-09-04","xrefs":[{"hgnc":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11998","ensembl":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000141510","uniprot":"https://www.uniprot.org/uniprotkb/P04637/entry","alphafold-db":"https://alphafold.ebi.ac.uk/entry/P04637","chembl":"https://www.ebi.ac.uk/chembl/explore/target/CHEMBL4096","open-targets":"https://platform.opentargets.org/target/ENSG00000141510","civic":"https://civicdb.org/genes/7157/summary","oncokb":"https://www.oncokb.org/gene/TP53","cosmic":"https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=TP53","cbioportal":"https://www.cbioportal.org/results/mutations?cancer_study_list=msk_impact_2017&gene_list=TP53","depmap":"https://depmap.org/portal/gene/TP53?tab=overview","human-protein-atlas":"https://www.proteinatlas.org/ENSG00000141510-TP53","ncbi-gene":"https://www.ncbi.nlm.nih.gov/gene/7157","omim":"https://www.omim.org/entry/191170"}],"products":[{"id":"eprenetapopt","name":"Eprenetapopt","status":"negative","modality":"Small 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Myelofibrosis","nct":"NCT04562389","phase":"3","status":"active"},{"id":"nct06472245","name":"Trial of Therapeutic Cancer Vaccine OSE2101 in Patients With Non-Small Cell Lung Cancer and Secondary Resistance to Immune Checkpoint Inhibitor","nct":"NCT06472245","phase":"3","status":"recruiting"},{"id":"nct04442022","name":"A Study of Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP) With or Without Selinexor in Patients With Relapsed/Refractory Diffuse Large B-cell Ly","nct":"NCT04442022","phase":"2/3","status":"active"},{"id":"nct05797831","name":"Study of Navtemadlin as Maintenance Therapy in TP53WT Advanced or Recurrent Endometrial Cancer","nct":"NCT05797831","phase":"2/3","status":"recruiting"},{"id":"nct04414475","name":"A Study of Selinexor (Seli) + Low-dose Dexamethasone (LDD) in Penta-refractory Multiple Myeloma (MM), Seli and Bortezomib + LDD in Triple-class Refrac","nct":"NCT04414475","phase":"2","status":"recruiting"},{"id":"nct03669965","name":"KRT-232 Compared to Ruxolitinib in Patients With Phlebotomy-Dependent Polycythemia Vera","nct":"NCT03669965","phase":"2","status":"active"},{"id":"nct03268382","name":"p53 Activation in Platinum-Resistant High Grade Serous Ovarian Cancer, a Study of PLD With APR-246","nct":"NCT03268382","phase":"2","status":"completed"},{"id":"nct02227251","name":"Selinexor (KPT-330) in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)","nct":"NCT02227251","phase":"2","status":"active"},{"id":"nct04782687","name":"Study of Selinexor Plus DRd for Newly Diagnosed Multiple Myeloma","nct":"NCT04782687","phase":"2","status":"active"},{"id":"nct06813079","name":"Using Tumor Models to Determine Treatments","nct":"NCT06813079","phase":"2","status":"recruiting"},{"id":"nct07060989","name":"A Study of Safety, Tolerability and Preliminary Efficacy of NTS071 in Subjects With Advanced Solid Tumors Harboring a TP53 Y220C Mutation","nct":"NCT07060989","phase":"1/2","status":"recruiting"},{"id":"nct05751798","name":"Dose-finding and Dose Expansion Study of OSE-279 in Subjects With Advanced Solid Tumors or Lymphomas","nct":"NCT05751798","phase":"1/2","status":"recruiting"},{"id":"nct04502394","name":"Safety and Efficacy of KRT-232 in Combination With Acalabrutinib in Subjects With R/R DLBCL or R/R CLL","nct":"NCT04502394","phase":"1/2","status":"recruiting"},{"id":"nct05035745","name":"Selinexor & Talazoparib in Advanced Refractory Solid Tumors; Advanced/Metastatic Triple Negative Breast Cancer (START)","nct":"NCT05035745","phase":"1/2","status":"recruiting"},{"id":"nct02343042","name":"Selinexor and Backbone Treatments of Multiple Myeloma Patients","nct":"NCT02343042","phase":"1/2","status":"recruiting"}],"pathways":["basal-cell-carcinoma-signalling","breast-cancer-signalling","senescence","chromosomal-instability","cml-signalling","clonal-evolution","clonal-haematopoiesis","colorectal-cancer-signalling","replication-stress","oncogene-activation-two-hit","endometrial-cancer-signalling","field-cancerisation","gastric-cancer-signalling","hepatocellular-carcinoma-signalling","lineage-plasticity-neuroendocrine","micrornas-in-cancer","mitotic-spindle-checkpoint","nsclc-signalling","oncogenic-viruses","p53-cell-cycle","pancreatic-cancer-signalling","sclc-signalling","synthetic-lethality-map","cell-cycle-engine-cdks","p53-mdm2-axis","thyroid-cancer-signalling"],"companies":["antengene","aprea-therapeutics","bulsara-bioworks","debiopharm","finaldose","kartos-therapeutics","karyopharm","nested-therapeutics","ose-immunotherapeutics","photys-therapeutics"],"keyPapers":["paper-garate-calderon-gallbladder-cancer-worldwide-exome-ebiomedicine-2026","paper-suryavanshi-indian-gallbladder-genomics-jco-go-2025","paper-zhu-population-specific-immunogenomics-gallbladder-cancer-mod-pathol-2025","paper-erices-chilean-gallbladder-landscape-front-oncol-2025","paper-giraldo-gallbladder-msk-impact-ccr-2022","paper-stopsack-prostate-genomes-by-race-ccr-2022","paper-philip-kras-wild-type-pancreatic-ccr-2022","paper-zhang-lung-cancer-never-smokers-nat-genet-2021","paper-nepal-gallbladder-microenvironment-subtypes-j-hepatol-2021","paper-wright-lymphgen-genetic-subtypes-dlbcl-cancer-cell-2020","paper-chen-east-asian-lung-adenocarcinoma-nat-genet-2020","paper-mateo-genomics-lethal-prostate-diagnosis-castration-resistance-jci-2020","paper-stopsack-mcspc-genomic-alterations-outcomes-ccr-2020","paper-cavallone-tnbc-ctdna-neoadjuvant-sci-rep-2020","paper-offin-rb1-tp53-transformation-risk-jto-2019","paper-marcoux-egfr-small-cell-transformation-outcomes-jco-2019","paper-bertucci-metastatic-breast-genomics-nature-2019","paper-abida-genomic-correlates-outcome-mcrpc-pnas-2019","paper-omori-ipmn-progression-pathways-gastroenterology-2019","paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019","paper-singhi-targeted-genome-profiling-3594-pdac-gastroenterology-2019","paper-hu-germline-mutations-pancreatic-cancer-risk-jama-2018","paper-qian-driver-genes-outcomes-resected-pancreatic-jama-oncol-2018","paper-annala-ctdna-resistance-abiraterone-enzalutamide-cancer-discov-2018","paper-loree-tumour-location-continuum-colorectal-ccr-2018","paper-arbour-kras-co-mutation-outcomes-ccr-2018","paper-quigley-structural-variation-mcrpc-cell-2018","paper-zheng-nigerian-inherited-breast-cancer-jco-2018","paper-felsenstein-ipmn-cooccurring-cancer-relatedness-gut-2018","paper-chapuy-molecular-subtypes-dlbcl-nat-med-2018","paper-tauriello-tgfbeta-immune-evasion-colorectal-nature-2018","paper-shimelis-tnbc-risk-genes-jnci-2018","paper-bareche-tnbc-multiomic-heterogeneity-ann-oncol-2018","paper-lee-clonal-history-small-cell-transformation-jco-2017","paper-huo-tcga-ancestry-breast-jama-oncol-2017","paper-wyatt-ctdna-tissue-concordance-mcrpc-jnci-2017","paper-tcga-pancreatic-integrated-characterisation-cancer-cell-2017","paper-ku-rb1-trp53-lineage-plasticity-science-2017","paper-mu-sox2-lineage-plasticity-science-2017","paper-tracerx-100-nejm-2017","paper-notta-punctuated-evolution-pancreatic-nature-2016","paper-javle-biliary-ngs-cancer-2016","paper-aparicio-aggressive-variant-prostate-tumour-suppressors-ccr-2016","paper-campbell-pan-lung-somatic-alterations-nat-genet-2016","paper-beltran-nepc-divergent-evolution-nat-med-2016","paper-bailey-molecular-subtypes-pancreatic-nature-2016","paper-alexandrov-tobacco-smoking-mutational-signatures-science-2016","paper-springer-pancreatic-cyst-molecular-classification-gastroenterology-2015","paper-skoulidis-kras-co-mutation-subsets-cancer-discov-2015","paper-george-sclc-genomic-profiles-nature-2015","paper-martincorena-somatic-mutations-normal-skin-science-2015","paper-scanu-salmonella-gallbladder-transformation-cell-host-microbe-2015","paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015","paper-tcga-molecular-taxonomy-primary-prostate-cell-2015","paper-gundem-evolutionary-history-lethal-metastatic-prostate-nature-2015","paper-waddell-whole-genomes-pancreatic-nature-2015","paper-tcga-lung-adenocarcinoma-nature-2014","paper-li-gallbladder-exome-erbb-nat-genet-2014","paper-vogelstein-cancer-genome-landscapes-science-2013","paper-tcga-lung-squamous-nature-2012","paper-tcga-colorectal-comprehensive-characterization-nature-2012","paper-tcga-breast-molecular-portraits-nature-2012","paper-biankin-pancreatic-exomes-axon-guidance-nature-2012","paper-shah-tnbc-clonal-evolution-nature-2012","paper-sequist-genotypic-histological-evolution-egfr-resistance-sci-transl-med-2011","paper-iacobuzio-donahue-dpc4-failure-pattern-autopsy-jco-2009","paper-jones-pancreatic-core-pathways-science-2008","paper-vogelstein-surfing-p53-network-nature-2000","paper-levine-p53-gatekeeper-cell-1997","paper-bischoff-onyx-015-science-1996","paper-el-deiry-waf1-p21-cell-1993","paper-hollstein-p53-mutations-science-1991","paper-fearon-cell","paper-vogelstein-genetic-alterations-colorectal-tumor-development-nejm-1988"],"hotspots":[{"label":"R175H","position":175,"kind":"loss-of-function","drugs":[]},{"label":"Y220C","position":220,"kind":"loss-of-function","frequency":"About 1.5% of TP53 mutations","drugs":[]},{"label":"R248Q / R248W","position":248,"kind":"loss-of-function","drugs":[]},{"label":"R273C / R273H","position":273,"kind":"loss-of-function","drugs":[]},{"label":"G245S / R249S / R282W","position":282,"kind":"loss-of-function","drugs":[]}],"openQuestions":[{"id":"tp53-drugging","question":"Can mutant p53 be drugged directly, whether by reactivation (Y220C binders), degradation, or synthetic lethality with WEE1 or ATR?","stage":"basic","actor":"research","source":{"label":"Vogelstein et al., Science 2013","url":"https://doi.org/10.1126/science.1235122"}}],"assays":[],"resistance":[{"class":"egfr-tki","mechanism":"Histologic transformation","category":"lineage"},{"class":"ar-pathway","mechanism":"Lineage plasticity to neuroendocrine prostate cancer","category":"lineage"}],"licence":"CC BY-NC 4.0, attribution to OnCo (https://onco.cc); commercial use needs a licence"}