{"entity":{"id":"pten","kind":"target","name":"PTEN","aka":["phosphatase and tensin homolog","MMAC1","TEP1"],"tldr":"PTEN is the brake on the PI3K growth pathway; when a tumour loses it the pathway runs unchecked, which is why PTEN loss now selects patients for the AKT inhibitor capivasertib.","summary":"PTEN is a lipid phosphatase that converts PIP3 back to PIP2, opposing PI3K and switching off AKT signalling. Loss through deletion, mutation or promoter silencing is common in prostate, endometrial, breast and brain tumours and in Cowden syndrome when inherited. Capivasertib's labels name PTEN alterations (with PIK3CA and AKT1) in breast cancer and PTEN deficiency by immunohistochemistry in prostate cancer, so the readout pages under this target carry both the sequencing and the IHC rules.","asOf":"2026-09-23","wikipedia":"https://en.wikipedia.org/wiki/PTEN_(gene)","links":[{"label":"HGNC HGNC:9588","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9588"},{"label":"UniProt P60484","url":"https://www.uniprot.org/uniprotkb/P60484/entry"}],"tags":["biomarker-parent","tumor-suppressor"],"related":["pten-alteration"],"cancers":["prostate-mhspc","breast-hr-positive","endometrial","glioblastoma","tnbc","colorectal","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":["capivasertib"],"companies":[],"institutions":[],"pathways":[],"terms":["pten-loss"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-tcga-breast-molecular-portraits-nature-2012","paper-barroso-sousa-tmb-pten-ici-mtnbc-ccr-2020","paper-loree-tumour-location-continuum-colorectal-ccr-2018","paper-ferraldeschi-pten-protein-loss-abiraterone-eur-urol-2015","paper-ipatential150-ipatasertib-abiraterone-pten-lancet-2021"],"journals":[],"dependsOn":[],"notes":["Triple-negative breast cancer: PTEN mutation or loss in up to 35% of basal-like tumours (Cancer Genome Atlas 2012) and deep deletion in 21% of 119 TCGA triple-negative samples (cBioPortal); PTEN alterations went with a 6% response rate to checkpoint inhibitors against 48% (Barroso-Sousa 2020) and defined the PTEN-low co-primary population of LOTUS (Kim 2017).","Colorectal cancer: inactivating mutation in 6 to 8% with deep deletion on top (cBioPortal); prevalence differs by precise tumour subsite (Loree 2018). No colorectal approval depends on PTEN status."],"symbol":"PTEN","role":["drug-target","oncogene-driver","tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[],"specificity":"tumour-specific","distribution":"few-types","specificityNote":"Tumour-specific alteration: 1 of 1 label readouts filed under it measure a sequence variant (PTEN alteration (sequencing) and PTEN loss (IHC)) absent from normal cells. HPA PTEN: RNA low tissue specificity; high antibody staining in 14 normal tissues; highest cancer staining head and neck cancer (2 of 4 high). Distribution: 4 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Prostate cancer, Breast cancer (all types), Endometrial cancer, Brain and spinal cord tumours (all types)); Open Targets associates it with 34 specific cancer types at or above 0.5 (PTEN hamartoma tumor syndrome, glioma susceptibility 2, Bannayan-Riley-Ruvalcaba syndrome, glioma, endometrial cancer, melanoma and more). (Rule 3 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"PTEN alteration (sequencing) and PTEN loss (IHC) label threshold","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d698c106-2322-401e-b738-cbd83c843ecf","note":"PTEN alteration (with PIK3CA and AKT1 as the qualifying set)"},{"label":"Human Protein Atlas PTEN tissue","url":"https://www.proteinatlas.org/ENSG00000171862-PTEN/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000171862 associations","url":"https://platform.opentargets.org/target/ENSG00000171862/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:9588","ensembl":"ENSG00000171862","uniprot":"P60484","entrez":"5728","firstDescribed":1997,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Li D.M. et al, Cancer Res, 1997, \"TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/9187108/","biology":"PTEN loss raises PIP3 and constitutively activates AKT and mTOR; it also has nuclear roles in genome stability, so PTEN-null tumours accumulate further damage.","whereFound":["Prostate cancer (loss in about 40 percent of metastatic disease)","Endometrial cancer","Glioblastoma","Breast cancer (PI3K pathway alterations)","Triple-negative breast cancer: mutation or deletion (loss) 12-35%","Colorectal cancer: inactivating mutation or deep deletion 6-8%","Prostate cancer: deep deletion, and inactivating mutation on top of it 12-41% depending on disease state"],"targetClass":"tumor-suppressor","prevalence":[{"cancerId":"tnbc","pct":"12-35","measure":"Mutation or deletion (loss)","source":"https://doi.org/10.1038/nature11412","note":"PTEN mutation or loss in 35% of basal-like tumours, with INPP4B loss in 30% (Cancer Genome Atlas 2012); cBioPortal: deep deletion in 25 of 119, 21.0%, and mutation in 8 of 123, 6.5%, in brca_tcga_pan_can_atlas_2018; mutation in 18 of 299, 6.0%, and deep deletion in 16 of 320, 5.0%, in brca_metabric; mutation in 15 of 176, 8.5%, and deep deletion in 10 of 176, 5.7%, in breast_msk_2018. PTEN alterations (mutation or one- or two-copy deletion) in 29% of 62 metastatic TNBC patients treated with checkpoint inhibitors, where they went with a 6% versus 48% response rate (Barroso-Sousa 2020, Clin Cancer Res)."},{"cancerId":"colorectal","pct":"6-8","measure":"Inactivating mutation or deep deletion","source":"https://www.cbioportal.org/study/summary?id=crc_msk_2026","note":"cBioPortal: mutation in 446 of 7,237, 6.2%, plus deep deletion in 70, in crc_msk_2026; 68 of 1,134, 6.0%, plus 19 deletions, in crc_msk_2017; 34 of 534, 6.4%, plus 17 deletions of 592, in coadread_tcga_pan_can_atlas_2018; 51 of 619, 8.2%, in coadread_dfci_2016. PTEN mutation prevalence differs by side and by precise location (Loree 2018)."},{"cancerId":"prostate","pct":"12-41","measure":"Deep deletion, and inactivating mutation on top of it","source":"https://www.cbioportal.org/study/summary?id=prad_tcga_pan_can_atlas_2018","note":"cBioPortal deep deletion: 85 of 489, 17.4%, in prad_tcga_pan_can_atlas_2018; 50 of 333, 15.0%, in prad_tcga_pub; 124 of 1,013, 12.2%, in prad_p1000; 61 of 424, 14.4%, in prad_mcspc_mskcc_2020; 262 of 2,260, 11.6%, in prostate_msk_2024; 209 of 1,465, 14.3%, in prad_cdk12_mskcc_2020; 114 of 444, 25.7%, in prad_su2c_2019; 41 of 150, 27.3%, in prad_su2c_2015; 55 of 149, 36.9%, in prad_fhcrc; 25 of 61, 41.0%, in prad_mich. Inactivating mutation adds 3 to 11% on top (182 of 2,260, 8.1%, in prostate_msk_2024; 46 of 424, 10.8%, in prad_mcspc_mskcc_2020)."}]},"route":"/targets/pten/","neighbours":{"biomarker":[{"id":"pten-alteration","kind":"biomarker","name":"PTEN alteration (sequencing) and PTEN loss (IHC)","route":"/biomarkers/pten-alteration/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"glioblastoma","kind":"cancer","name":"Glioma & glioblastoma","route":"/cancers/glioblastoma/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"prostate-mhspc","kind":"cancer","name":"Metastatic hormone-sensitive prostate cancer","route":"/cancers/prostate-mhspc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"drug":[{"id":"capivasertib","kind":"drug","name":"Capivasertib","route":"/drugs/capivasertib/"}],"term":[{"id":"pten-loss","kind":"term","name":"PTEN loss","route":"/terms/pten-loss/"}],"paper":[{"id":"paper-schmid-pakt-capivasertib-tnbc-jco-2020","kind":"paper","name":"Capivasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer: the PAKT trial","route":"/key-papers/paper-schmid-pakt-capivasertib-tnbc-jco-2020/"},{"id":"paper-loree-tumour-location-continuum-colorectal-ccr-2018","kind":"paper","name":"Classifying colorectal cancer by tumor location rather than sidedness highlights a continuum in mutation profiles and consensus molecular subtypes","route":"/key-papers/paper-loree-tumour-location-continuum-colorectal-ccr-2018/"},{"id":"paper-aparicio-aggressive-variant-prostate-tumour-suppressors-ccr-2016","kind":"paper","name":"Combined tumour suppressor defects characterise clinically defined aggressive variant prostate cancers","route":"/key-papers/paper-aparicio-aggressive-variant-prostate-tumour-suppressors-ccr-2016/"},{"id":"paper-tcga-lung-squamous-nature-2012","kind":"paper","name":"Comprehensive genomic characterization of squamous cell lung cancers","route":"/key-papers/paper-tcga-lung-squamous-nature-2012/"},{"id":"paper-george-sclc-genomic-profiles-nature-2015","kind":"paper","name":"Comprehensive genomic profiles of small cell lung cancer","route":"/key-papers/paper-george-sclc-genomic-profiles-nature-2015/"},{"id":"paper-tcga-breast-molecular-portraits-nature-2012","kind":"paper","name":"Comprehensive molecular portraits of human breast tumours","route":"/key-papers/paper-tcga-breast-molecular-portraits-nature-2012/"},{"id":"paper-wyatt-ctdna-tissue-concordance-mcrpc-jnci-2017","kind":"paper","name":"Concordance of circulating tumour DNA and matched metastatic tissue biopsy in prostate cancer","route":"/key-papers/paper-wyatt-ctdna-tissue-concordance-mcrpc-jnci-2017/"},{"id":"paper-stopsack-prostate-genomes-by-race-ccr-2022","kind":"paper","name":"Differences in prostate cancer genomes by self-reported race","route":"/key-papers/paper-stopsack-prostate-genomes-by-race-ccr-2022/"},{"id":"paper-mateo-genomics-lethal-prostate-diagnosis-castration-resistance-jci-2020","kind":"paper","name":"Genomics of lethal prostate cancer at diagnosis and castration resistance","route":"/key-papers/paper-mateo-genomics-lethal-prostate-diagnosis-castration-resistance-jci-2020/"},{"id":"paper-kim-lotus-ipatasertib-tnbc-lancet-oncol-2017","kind":"paper","name":"Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial","route":"/key-papers/paper-kim-lotus-ipatasertib-tnbc-lancet-oncol-2017/"},{"id":"paper-ipatential150-ipatasertib-abiraterone-pten-lancet-2021","kind":"paper","name":"IPATential150: ipatasertib plus abiraterone and prednisolone in metastatic castration-resistant prostate cancer","route":"/key-papers/paper-ipatential150-ipatasertib-abiraterone-pten-lancet-2021/"},{"id":"paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019","kind":"paper","name":"Prospective comprehensive genomic profiling of 3,476 primary and metastatic prostate tumours","route":"/key-papers/paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019/"},{"id":"paper-ferraldeschi-pten-protein-loss-abiraterone-eur-urol-2015","kind":"paper","name":"PTEN protein loss and clinical outcome from castration-resistant prostate cancer treated with abiraterone acetate","route":"/key-papers/paper-ferraldeschi-pten-protein-loss-abiraterone-eur-urol-2015/"},{"id":"paper-ku-rb1-trp53-lineage-plasticity-science-2017","kind":"paper","name":"Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis and antiandrogen resistance","route":"/key-papers/paper-ku-rb1-trp53-lineage-plasticity-science-2017/"},{"id":"paper-carver-pi3k-ar-reciprocal-feedback-prostate-cancer-cell-2011","kind":"paper","name":"Reciprocal feedback regulation of PI3K and androgen receptor signalling in PTEN-deficient prostate cancer","route":"/key-papers/paper-carver-pi3k-ar-reciprocal-feedback-prostate-cancer-cell-2011/"},{"id":"paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015","kind":"paper","name":"SU2C-PCF: integrative clinical genomics of advanced prostate cancer","route":"/key-papers/paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015/"},{"id":"paper-tcga-molecular-taxonomy-primary-prostate-cell-2015","kind":"paper","name":"TCGA: the molecular taxonomy of primary prostate cancer","route":"/key-papers/paper-tcga-molecular-taxonomy-primary-prostate-cell-2015/"},{"id":"paper-shah-tnbc-clonal-evolution-nature-2012","kind":"paper","name":"The clonal and mutational evolution spectrum of primary triple-negative breast cancers","route":"/key-papers/paper-shah-tnbc-clonal-evolution-nature-2012/"},{"id":"paper-barroso-sousa-tmb-pten-ici-mtnbc-ccr-2020","kind":"paper","name":"Tumor mutational burden and PTEN alterations as molecular correlates of response to PD-1/L1 blockade in metastatic triple-negative breast cancer","route":"/key-papers/paper-barroso-sousa-tmb-pten-ici-mtnbc-ccr-2020/"},{"id":"paper-bareche-tnbc-multiomic-heterogeneity-ann-oncol-2018","kind":"paper","name":"Unravelling triple-negative breast cancer molecular heterogeneity using an integrative multiomic analysis","route":"/key-papers/paper-bareche-tnbc-multiomic-heterogeneity-ann-oncol-2018/"}],"trial":[{"id":"nct03997123","kind":"trial","name":"Capivasertib+Paclitaxel as First Line Treatment for Patients With Locally Advanced or Metastatic TNBC","route":"/trials/nct03997123/"},{"id":"imbassador250","kind":"trial","name":"IMbassador250","route":"/trials/imbassador250/"},{"id":"ipatunity130","kind":"trial","name":"IPATunity130","route":"/trials/ipatunity130/"},{"id":"lotus","kind":"trial","name":"LOTUS","route":"/trials/lotus/"},{"id":"pakt","kind":"trial","name":"PAKT","route":"/trials/pakt/"}],"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}]}}