{"entity":{"id":"estrogen-receptor","kind":"target","name":"Estrogen receptor (ERα)","aka":[],"tldr":"The hormone switch that drives most breast cancers. Blocking or destroying it is the oldest and most effective targeted therapy.","summary":"Tamoxifen (SERM), aromatase inhibitors, fulvestrant (SERD), oral SERDs (elacestrant, imlunestrant, camizestrant), and the PROTAC degrader vepdegestrant (approved 2026 for ESR1-mutant disease) form the endocrine armamentarium. ESR1 mutations arise under aromatase-inhibitor pressure and are detected by ctDNA.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Estrogen_receptor_alpha","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Estrogen_receptor_alpha"}],"tags":["hormonal"],"related":["er-status","esr1-mutation-ctdna"],"cancers":["breast-hr-positive","endometrial"],"sections":[],"technologies":[],"targets":[],"drugs":["fluoroestradiol-f18","guardant360-cdx","toremifene","raloxifene","lns8801"],"companies":[],"institutions":[],"pathways":["er-signaling","breast-cancer-signalling","chemical-carcinogenesis-receptor-activation","endometrial-cancer-signalling"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"ESR1","role":[],"sources":[],"specificity":"tumour-associated","distribution":"few-types","specificityNote":"Tumour-associated overexpression: HPA finds the RNA cancer enhanced in cancer (Breast Invasive Carcinoma (TCGA), Uterine Corpus Endometrial Carcinoma (TCGA)) and tissue enhanced in normal cervix, endometrium 1, fallopian tube, so the tumour and the normal tissue it comes from share the target and the medicine relies on the difference in level. HPA ESR1: RNA tissue enhanced (cervix 81 nTPM, endometrium 1 104 nTPM, fallopian tube 61 nTPM); high antibody staining in 3 normal tissues; highest cancer staining breast cancer (7 of 10 high). Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Breast cancer (all types), Endometrial cancer); approvals of single-target medicines aimed at it also list Ovarian cancer, not counted; Open Targets associates it with 4 specific cancer types at or above 0.5 (breast cancer, breast carcinoma, breast adenocarcinoma, prostate cancer). (Rule 7 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas ESR1 tissue","url":"https://www.proteinatlas.org/ENSG00000091831-ESR1/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas ESR1 pathology","url":"https://www.proteinatlas.org/ENSG00000091831-ESR1/pathology","note":"patients per staining level per cancer type (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000091831 associations","url":"https://platform.opentargets.org/target/ENSG00000091831/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:3467","ensembl":"ENSG00000091831","uniprot":"P03372","entrez":"2099","firstDescribed":1986,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Green et al, Nature, 1986, \"Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/3754034/","biology":"Ligand-activated nuclear receptor; ESR1 Y537S/D538G mutations render it ligand-independent.","whereFound":["HR+ breast cancer (~70% of breast cancers)","Endometrial","Ovarian (low-grade serous)"],"targetClass":"nuclear-receptor","prevalence":[{"cancerId":"breast-hr-positive","pct":100,"measure":"ER+ (>=1% IHC), defining","source":"https://en.wikipedia.org/wiki/Estrogen_receptor_alpha","note":"~70% of all breast cancers; ESR1 mutation ~30% after AI"},{"cancerId":"endometrial","pct":"70-80","measure":"ER expression (endometrioid)","source":"https://en.wikipedia.org/wiki/Estrogen_receptor_alpha"}]},"route":"/targets/estrogen-receptor/","neighbours":{"biomarker":[{"id":"er-status","kind":"biomarker","name":"ER status (oestrogen receptor by IHC)","route":"/biomarkers/er-status/"},{"id":"esr1-mutation-ctdna","kind":"biomarker","name":"ESR1 mutation (ligand-binding domain, usually in ctDNA)","route":"/biomarkers/esr1-mutation-ctdna/"}],"cancer":[{"id":"ductal-carcinoma-in-situ","kind":"cancer","name":"Ductal carcinoma in situ (DCIS)","route":"/cancers/ductal-carcinoma-in-situ/"},{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"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":"uterine-sarcoma","kind":"cancer","name":"Uterine sarcoma","route":"/cancers/uterine-sarcoma/"}],"drug":[{"id":"camizestrant","kind":"drug","name":"Camizestrant","route":"/drugs/camizestrant/"},{"id":"diethylstilbestrol","kind":"drug","name":"Diethylstilbestrol","route":"/drugs/diethylstilbestrol/"},{"id":"elacestrant","kind":"drug","name":"Elacestrant","route":"/drugs/elacestrant/"},{"id":"exemestane","kind":"drug","name":"Exemestane","route":"/drugs/exemestane/"},{"id":"fluoroestradiol-f18","kind":"drug","name":"Fluoroestradiol F-18 (FES PET)","route":"/drugs/fluoroestradiol-f18/"},{"id":"fulvestrant","kind":"drug","name":"Fulvestrant","route":"/drugs/fulvestrant/"},{"id":"giredestrant","kind":"drug","name":"Giredestrant","route":"/drugs/giredestrant/"},{"id":"goserelin","kind":"drug","name":"Goserelin / leuprolide (ovarian function suppression)","route":"/drugs/goserelin/"},{"id":"guardant360-cdx","kind":"drug","name":"Guardant360 CDx","route":"/drugs/guardant360-cdx/"},{"id":"imlunestrant","kind":"drug","name":"Imlunestrant","route":"/drugs/imlunestrant/"},{"id":"letrozole","kind":"drug","name":"Letrozole (and other aromatase inhibitors)","route":"/drugs/letrozole/"},{"id":"lns8801","kind":"drug","name":"LNS8801","route":"/drugs/lns8801/"},{"id":"megestrol-progestins","kind":"drug","name":"Progestins (megestrol acetate, medroxyprogesterone, levonorgestrel IUD)","route":"/drugs/megestrol-progestins/"},{"id":"raloxifene","kind":"drug","name":"Raloxifene","route":"/drugs/raloxifene/"},{"id":"tamoxifen","kind":"drug","name":"Tamoxifen","route":"/drugs/tamoxifen/"},{"id":"toremifene","kind":"drug","name":"Toremifene","route":"/drugs/toremifene/"},{"id":"vepdegestrant","kind":"drug","name":"Vepdegestrant","route":"/drugs/vepdegestrant/"}],"pathway":[{"id":"breast-cancer-signalling","kind":"pathway","name":"Breast cancer (KEGG map)","route":"/pathways/breast-cancer-signalling/"},{"id":"chemical-carcinogenesis-receptor-activation","kind":"pathway","name":"Chemical carcinogenesis - receptor activation","route":"/pathways/chemical-carcinogenesis-receptor-activation/"},{"id":"endometrial-cancer-signalling","kind":"pathway","name":"Endometrial cancer (KEGG map)","route":"/pathways/endometrial-cancer-signalling/"},{"id":"lipid-metabolism-cancer","kind":"pathway","name":"Lipid synthesis, uptake & cholesterol","route":"/pathways/lipid-metabolism-cancer/"},{"id":"er-signaling","kind":"pathway","name":"Oestrogen receptor signalling","route":"/pathways/er-signaling/"},{"id":"resistance-routes-map","kind":"pathway","name":"Resistance routes: how a blocked pathway comes back","route":"/pathways/resistance-routes-map/"},{"id":"cell-cycle-engine-cdks","kind":"pathway","name":"The cell-cycle engine (cyclins & CDKs)","route":"/pathways/cell-cycle-engine-cdks/"},{"id":"transcription-addiction","kind":"pathway","name":"Transcriptional machinery & addiction","route":"/pathways/transcription-addiction/"},{"id":"ubiquitin-proteasome-system","kind":"pathway","name":"Ubiquitin-proteasome system & protein homeostasis","route":"/pathways/ubiquitin-proteasome-system/"}],"trial":[{"id":"ember-3","kind":"trial","name":"EMBER-3","route":"/trials/ember-3/"},{"id":"emerald","kind":"trial","name":"EMERALD","route":"/trials/emerald/"},{"id":"evera","kind":"trial","name":"evERA","route":"/trials/evera/"},{"id":"lidera","kind":"trial","name":"lidERA","route":"/trials/lidera/"},{"id":"monaleesa-2","kind":"trial","name":"MONALEESA-2","route":"/trials/monaleesa-2/"},{"id":"serena-6","kind":"trial","name":"SERENA-6","route":"/trials/serena-6/"},{"id":"veritac-2","kind":"trial","name":"VERITAC-2","route":"/trials/veritac-2/"}],"term":[{"id":"agonist-antagonist","kind":"term","name":"Agonist and antagonist","route":"/terms/agonist-antagonist/"},{"id":"chemoprevention-and-er-negative-breast-cancer","kind":"term","name":"Chemoprevention (tamoxifen, anastrozole, raloxifene) and ER-negative breast cancer","route":"/terms/chemoprevention-and-er-negative-breast-cancer/"},{"id":"endocrine-resistance","kind":"term","name":"Endocrine resistance","route":"/terms/endocrine-resistance/"},{"id":"endocrine-therapy-resistance","kind":"term","name":"Endocrine therapy and endocrine resistance","route":"/terms/endocrine-therapy-resistance/"},{"id":"esr1-mutation","kind":"term","name":"ESR1 mutation","route":"/terms/esr1-mutation/"},{"id":"hormone-receptor-status","kind":"term","name":"Hormone receptor status (ER / PR)","route":"/terms/hormone-receptor-status/"},{"id":"hormone-therapy","kind":"term","name":"Hormone therapy","route":"/terms/hormone-therapy/"},{"id":"oral-serd","kind":"term","name":"Oral SERD","route":"/terms/oral-serd/"},{"id":"receptor","kind":"term","name":"Receptor","route":"/terms/receptor/"},{"id":"serd","kind":"term","name":"Selective oestrogen receptor degrader (SERD)","route":"/terms/serd/"}],"technology":[{"id":"cdk46-inhibitor","kind":"technology","name":"CDK4/6 inhibitors","route":"/technologies/cdk46-inhibitor/"},{"id":"chemoprevention","kind":"technology","name":"Chemoprevention & risk-reducing surgery","route":"/technologies/chemoprevention/"},{"id":"endocrine-therapy","kind":"technology","name":"Endocrine therapy (SERMs, AIs, SERDs)","route":"/technologies/endocrine-therapy/"},{"id":"fes-pet","kind":"technology","name":"FES PET (oestrogen receptor imaging)","route":"/technologies/fes-pet/"},{"id":"protac-degrader","kind":"technology","name":"PROTACs & molecular glues (targeted protein degradation)","route":"/technologies/protac-degrader/"}],"target":[{"id":"pgr","kind":"target","name":"Progesterone receptor (PGR)","route":"/targets/pgr/"}],"person":[{"id":"aditya-bardia","kind":"person","name":"Aditya Bardia","route":"/people/aditya-bardia/"},{"id":"debu-tripathy","kind":"person","name":"Debu Tripathy","route":"/people/debu-tripathy/"},{"id":"francois-clement-bidard","kind":"person","name":"François-Clément Bidard","route":"/people/francois-clement-bidard/"},{"id":"komal-jhaveri","kind":"person","name":"Komal Jhaveri","route":"/people/komal-jhaveri/"},{"id":"massimo-cristofanilli","kind":"person","name":"Massimo Cristofanilli","route":"/people/massimo-cristofanilli/"},{"id":"matthew-goetz","kind":"person","name":"Matthew P. Goetz","route":"/people/matthew-goetz/"},{"id":"mitch-dowsett","kind":"person","name":"Mitch Dowsett","route":"/people/mitch-dowsett/"},{"id":"nicholas-turner","kind":"person","name":"Nicholas Turner","route":"/people/nicholas-turner/"},{"id":"im-seock-ah","kind":"person","name":"Seock-Ah Im","route":"/people/im-seock-ah/"},{"id":"stephen-johnston","kind":"person","name":"Stephen Johnston","route":"/people/stephen-johnston/"}],"idea":[{"id":"idea-bio1-baseline-ultradeep-resistant-clones","kind":"idea","name":"Look for the resistant sub-population before the first dose","route":"/ideas/idea-bio1-baseline-ultradeep-resistant-clones/"},{"id":"idea-prev-low-dose-tamoxifen-uptake","kind":"idea","name":"Low-dose tamoxifen for high-risk women, prescribed by pharmacists and nurses","route":"/ideas/idea-prev-low-dose-tamoxifen-uptake/"},{"id":"idea-bio1-resistance-mutation-vaccine","kind":"idea","name":"Vaccinate against the resistance mutation before it takes over","route":"/ideas/idea-bio1-resistance-mutation-vaccine/"}],"paper":[{"id":"paper-ibis-i-tamoxifen-lancet-oncol-2015","kind":"paper","name":"IBIS-I: five years of tamoxifen keeps preventing breast cancer for at least 20 years","route":"/key-papers/paper-ibis-i-tamoxifen-lancet-oncol-2015/"},{"id":"paper-monarche-jco-2020","kind":"paper","name":"monarchE: two years of abemaciclib after surgery in high-risk, hormone-receptor-positive early breast cancer","route":"/key-papers/paper-monarche-jco-2020/"},{"id":"paper-natalee-nejm-2024","kind":"paper","name":"NATALEE: three years of ribociclib after surgery in a broad population of hormone-receptor-positive early breast cancer","route":"/key-papers/paper-natalee-nejm-2024/"},{"id":"paper-protac-concept-sakamoto-pnas-2001","kind":"paper","name":"The first PROTAC: a chimeric molecule that tags a protein for destruction","route":"/key-papers/paper-protac-concept-sakamoto-pnas-2001/"}],"institution":[{"id":"karmanos","kind":"institution","name":"Barbara Ann Karmanos Cancer Institute","route":"/institutions/karmanos/"},{"id":"beatson-glasgow","kind":"institution","name":"Beatson West of Scotland Cancer Centre / CRUK Scotland Institute","route":"/institutions/beatson-glasgow/"},{"id":"georgetown-lombardi","kind":"institution","name":"Georgetown Lombardi Comprehensive Cancer Center","route":"/institutions/georgetown-lombardi/"},{"id":"tohoku-university-hospital","kind":"institution","name":"Tohoku University Hospital","route":"/institutions/tohoku-university-hospital/"}],"company":[{"id":"pathos-ai","kind":"company","name":"Pathos AI","route":"/companies/pathos-ai/"}]}}