{"entity":{"id":"ar-signaling","kind":"pathway","name":"Androgen receptor signalling","aka":[],"tldr":"Androgen receptor signalling is prostate cancer's engine. Testosterone becomes DHT, binds the androgen receptor, and drives growth genes. Castration removes the fuel; newer pills block the receptor or the enzyme that makes fuel inside the tumour.","summary":"Testicular testosterone (and adrenal precursors converted intratumourally via CYP17A1) is reduced to DHT by 5α-reductase and binds AR, which translocates to the nucleus and drives PSA, TMPRSS2-ERG, and proliferation genes. GnRH agonists/antagonists shut testicular production; abiraterone blocks CYP17A1; enzalutamide, apalutamide, darolutamide block AR. Castration resistance arises via AR amplification, ligand-binding mutations, splice variants (AR-V7 lacks the ligand domain), glucocorticoid receptor substitution, and lineage plasticity to neuroendocrine phenotype.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Androgen_receptor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Androgen_receptor"}],"tags":[],"related":[],"cancers":["prostate","tnbc"],"sections":[],"technologies":["androgen-deprivation"],"targets":["androgen-receptor","parp","akt","psma"],"drugs":["capivasertib","olaparib","talazoparib","niraparib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"analogy":"Same key-and-lock idea as oestrogen: castration stops making keys, abiraterone shuts the tumour's own key factory, enzalutamide blocks the lock. AR-V7 is a lock with no keyhole that is permanently open.","nodes":[{"id":"gnrh","label":"GnRH → LH → testis","x":20,"y":8},{"id":"testo","label":"Testosterone","x":20,"y":28},{"id":"cyp17","label":"CYP17A1 (adrenal/intratumoural)","x":65,"y":15},{"id":"dht","label":"DHT","x":40,"y":45},{"id":"ar","label":"Androgen receptor","x":40,"y":62,"targetId":"androgen-receptor"},{"id":"arv7","label":"AR-V7 / amplification","x":80,"y":55},{"id":"genes","label":"PSA, TMPRSS2-ERG, growth genes","x":40,"y":80},{"id":"prol","label":"Proliferation","x":40,"y":96}],"edges":[{"from":"gnrh","to":"testo","type":"activates"},{"from":"cyp17","to":"testo","type":"activates"},{"from":"testo","to":"dht","type":"activates"},{"from":"dht","to":"ar","type":"activates"},{"from":"arv7","to":"ar","type":"activates"},{"from":"ar","to":"genes","type":"activates"},{"from":"genes","to":"prol","type":"activates"}],"interventions":["GnRH agonists/antagonists (leuprolide, relugolix)","CYP17A1 inhibitor abiraterone","AR antagonists enzalutamide, apalutamide, darolutamide","PARP inhibitors + ARPI in HRR-mutant disease; capivasertib + abiraterone in PTEN-deficient","AR degraders, N-terminal domain inhibitors (trials)"]},"route":"/pathways/ar-signaling/","neighbours":{"cancer":[{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"salivary-gland","kind":"cancer","name":"Salivary gland cancers","route":"/cancers/salivary-gland/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"androgen-deprivation","kind":"technology","name":"Androgen deprivation & AR pathway inhibitors","route":"/technologies/androgen-deprivation/"}],"target":[{"id":"akt","kind":"target","name":"AKT","route":"/targets/akt/"},{"id":"androgen-receptor","kind":"target","name":"Androgen receptor","route":"/targets/androgen-receptor/"},{"id":"parp","kind":"target","name":"PARP","route":"/targets/parp/"},{"id":"psma","kind":"target","name":"PSMA","route":"/targets/psma/"}],"drug":[{"id":"abiraterone","kind":"drug","name":"Abiraterone acetate","route":"/drugs/abiraterone/"},{"id":"apalutamide","kind":"drug","name":"Apalutamide","route":"/drugs/apalutamide/"},{"id":"bicalutamide","kind":"drug","name":"Bicalutamide","route":"/drugs/bicalutamide/"},{"id":"capivasertib","kind":"drug","name":"Capivasertib","route":"/drugs/capivasertib/"},{"id":"darolutamide","kind":"drug","name":"Darolutamide","route":"/drugs/darolutamide/"},{"id":"enzalutamide","kind":"drug","name":"Enzalutamide","route":"/drugs/enzalutamide/"},{"id":"niraparib","kind":"drug","name":"Niraparib","route":"/drugs/niraparib/"},{"id":"olaparib","kind":"drug","name":"Olaparib","route":"/drugs/olaparib/"},{"id":"relugolix","kind":"drug","name":"Relugolix","route":"/drugs/relugolix/"},{"id":"talazoparib","kind":"drug","name":"Talazoparib","route":"/drugs/talazoparib/"}],"term":[{"id":"ar-v7","kind":"term","name":"AR-V7 splice variant","route":"/terms/ar-v7/"},{"id":"castration-resistance","kind":"term","name":"Castration-resistant prostate cancer (CRPC)","route":"/terms/castration-resistance/"},{"id":"hormone-therapy","kind":"term","name":"Hormone therapy","route":"/terms/hormone-therapy/"},{"id":"signalling-pathway","kind":"term","name":"Signalling pathway","route":"/terms/signalling-pathway/"}],"paper":[{"id":"paper-bluemn-double-negative-prostate-fgf-mapk-cancer-cell-2017","kind":"paper","name":"Androgen receptor pathway-independent prostate cancer is sustained through FGF signalling","route":"/key-papers/paper-bluemn-double-negative-prostate-fgf-mapk-cancer-cell-2017/"},{"id":"paper-antonarakis-ar-v7-resistance-nejm-2014","kind":"paper","name":"AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer","route":"/key-papers/paper-antonarakis-ar-v7-resistance-nejm-2014/"},{"id":"paper-annala-ctdna-resistance-abiraterone-enzalutamide-cancer-discov-2018","kind":"paper","name":"Circulating tumour DNA genomics correlate with resistance to abiraterone and enzalutamide in prostate 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upstream enhancer)","route":"/biomarkers/ar-amplification/"},{"id":"ar-ligand-binding-domain-mutation","kind":"biomarker","name":"AR ligand-binding-domain mutation (L702H, W742C, H875Y, T878A, F877L)","route":"/biomarkers/ar-ligand-binding-domain-mutation/"},{"id":"spop-mutation","kind":"biomarker","name":"SPOP mutation","route":"/biomarkers/spop-mutation/"},{"id":"tmprss2-erg-fusion","kind":"biomarker","name":"TMPRSS2-ERG fusion (and the other ETS rearrangements)","route":"/biomarkers/tmprss2-erg-fusion/"},{"id":"nepc-transformation","kind":"biomarker","name":"Treatment-emergent neuroendocrine transformation (recognising it)","route":"/biomarkers/nepc-transformation/"}],"pairing":[{"id":"parp-plus-arpi","kind":"pairing","name":"PARP inhibitor + AR pathway inhibitor (prostate)","route":"/pairings/parp-plus-arpi/"}],"idea":[{"id":"idea-bio1-evolutionary-double-bind","kind":"idea","name":"Design drug pairs where resisting one makes you vulnerable to the other","route":"/ideas/idea-bio1-evolutionary-double-bind/"},{"id":"idea-bio1-arv7-degrader","kind":"idea","name":"Destroy the truncated androgen receptor that hormone drugs cannot touch","route":"/ideas/idea-bio1-arv7-degrader/"}],"pathway":[{"id":"lineage-plasticity-neuroendocrine","kind":"pathway","name":"Lineage plasticity & neuroendocrine transformation","route":"/pathways/lineage-plasticity-neuroendocrine/"},{"id":"prostate-cancer-signalling","kind":"pathway","name":"Prostate cancer (KEGG map)","route":"/pathways/prostate-cancer-signalling/"},{"id":"rna-splicing","kind":"pathway","name":"RNA splicing","route":"/pathways/rna-splicing/"},{"id":"transcription-addiction","kind":"pathway","name":"Transcriptional machinery & addiction","route":"/pathways/transcription-addiction/"}]}}