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The hormone switch that drives prostate cancer, attacked by castration and by pills that block the receptor. This dossier gathers the 19 products (11 approved), 116 trials, 5 pathways and 2 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
Nuclear receptor; amplification, splice variants (AR-V7), and ligand-binding-domain mutations drive resistance.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Prostate cancer | >95% | AR-driven at diagnosis | AR-V7 in ~20-40% of mCRPC | Wikipedia |
| Prostate cancer | 1-57% | High-level amplification of the gene, and of an upstream enhancer | cBioPortal high-level amplification: 5 of 489, 1.0%, in prad_tcga_pan_can_atlas_2018; 17 of 424, 4.0%, in prad_mcspc_mskcc_2020; 237 of 2,260, 10.5%, in prostate_msk_2024; 9 of 82, 11.0%, in the patient-contributed mpcproject_broad_2021; 217 of 444, 48.9%, in prad_su2c_2019; 78 of 150, 52.0%, in prad_su2c_2015; 85 of 149, 57.0%, in prad_fhcrc. High-level amplification of Xq11-q13 was found in 7 of 23 tumours recurring on androgen deprivation and none of the pre-treatment specimens from the same men (Visakorpi 1995); the upstream enhancer is amplified in 81% of 101 deeply sequenced castration-resistant genomes (Quigley 2018). | cBioPortal (TCGA) |
| Triple-negative breast cancer | 12-16% | AR expression and luminal androgen receptor subtype | LAR was 16% of tumours by TNBCtype-4 and 9% by the original six-subtype call (Lehmann 2016); 77 of 485 classifiable TNBCs, 16%, with 92% of LAR patients aged 45 or over (Bareche 2018); AR nuclear staining above 10% in 12% of 424 ER/PR-negative patients screened for TBCRC 011 (Gucalp 2013); 78 of 118 enrolled enzalutamide patients had 10% or more nuclear AR (Traina 2018). AR mutation is rare: 2 of 123 in brca_tcga_pan_can_atlas_2018 (cBioPortal). | doi.org |
| Triple-negative breast cancer | 10-15% | Luminal androgen receptor subtype | Wikipedia | |
| Prostate cancer | 0.4-18% | L702H, W742C/L, H875Y, T878A, F877L | cBioPortal samples with any AR mutation: 61 of 444, 13.7%, in prad_su2c_2019; 27 of 150, 18.0%, in prad_su2c_2015; 93 of 2,260, 4.1%, in prostate_msk_2024; 9 of 424, 2.1%, in prad_mcspc_mskcc_2020; 2 of 494, 0.4%, in prad_tcga_pan_can_atlas_2018. Allele records in prad_su2c_2019, 72 records: L702H 17, T878A 15, H875Y 11, W742C 8, W742L 4, F877L 3. | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
| Residue | Kind | How common | What it does | Addressed by | Defeats | Source |
|---|---|---|---|---|---|---|
| T878A 878 | Resistance | not sourced | Broadens ligand specificity so progesterone and the abiraterone metabolite become agonists; enriched after abiraterone. | Watson et al., Nat Rev Cancer 2015 | ||
| F877L 877 | Resistance | not sourced | Converts enzalutamide and apalutamide into agonists; darolutamide retains antagonism in preclinical models. | Watson et al., Nat Rev Cancer 2015 | ||
| L702H 702 | Resistance | not sourced | Makes glucocorticoids (prednisone given with abiraterone) into AR agonists. | Watson et al., Nat Rev Cancer 2015 | ||
| W742C / H875Y 742 | Resistance | not sourced | Bicalutamide-to-agonist and broad promiscuity mutations from the first-generation anti-androgen era. | Watson et al., Nat Rev Cancer 2015 | ||
| AR-V7 (splice variant, no LBD) 640 to 670 | Resistance | not sourced | Truncated after the DNA-binding domain, so no ligand-binding-domain drug can touch it; the case for N-terminal-domain binders and degraders. | none in corpus | Watson et al., Nat Rev Cancer 2015 |
Frequencies are quoted from the source on each row; a blank means no figure was sourced, not that it is rare. Domain boundaries are approximate. Sources for the map: COSMIC: AR.
| Modality | Approved | Phase 3 | Phase 2 | Withdrawn or failed |
|---|---|---|---|---|
| Small molecule 14 | ||||
| Degrader 3 | - | - | ||
| Non-steroidal antiandrogen 2 | - | - | - |
| Trial | Setting | Result | Products | ||
|---|---|---|---|---|---|
| 3 | Active | A Phase 3 Randomized, Placebo-controlled, Double-blind Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for the Treatment of Participants With Deleterious Germline or Somatic Homologous Recombination Repair (HRR) Gene-Mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC) | - | ||
PEACE-3 (EORTC 1333) NCT02194842 | 3 | Positive | Asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer with bone metastases: enzalutamide 160 mg daily alone against enzalutamide with six monthly injections of radium-223 at 55 kBq/kg, with bone-protecting agents made mandatory for all patients from March 2018, with radiological progression-free survival as the primary endpoint | Median overall survival 38.2 months with enzalutamide plus radium-223 against 32.6 months with enzalutamide alone (hazard ratio 0.76, 95 percent confidence interval 0.60 to 0.96, p=0.0096); radiological progression-free survival hazard ratio 0.71 (0.57 to 0.89). Bone-protecting agents mandatory. | |
CAPItello-281 NCT04493853 | 3 | Positive | De novo metastatic hormone-sensitive prostate cancer with PTEN deficiency: abiraterone + capivasertib vs abiraterone + placebo | Median rPFS 33.2 against 25.7 months, HR 0.81 (95% CI 0.66 to 0.98, p=0.034); OS HR 0.90 at 26.4% maturity; approved 2026. | |
KEYNOTE-641 NCT03834493 | 3 | Negative | Chemotherapy-naive metastatic castration-resistant prostate cancer, prior abiraterone permitted and prior docetaxel allowed only in the hormone-sensitive setting: pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles with enzalutamide 160 mg daily, with dual primary endpoints of overall survival and radiographic progression-free survival | Median overall survival 24.7 against 27.3 months (hazard ratio 1.04, 95 percent confidence interval 0.88 to 1.22) and radiographic progression-free survival 10.4 against 9.0 months (0.98, 0.84 to 1.14); stopped for futility. Grade 3 or higher treatment-related adverse events 31.2 against 10.8 percent. | |
KEYNOTE-991 NCT04191096 | 3 | Negative | Metastatic hormone-sensitive prostate cancer not previously treated with a next-generation hormonal agent: pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles with enzalutamide 160 mg daily and continuous androgen deprivation, with primary endpoints of radiographic progression-free survival and overall survival | Radiographic progression-free survival hazard ratio 1.20 (95 percent confidence interval 0.96 to 1.49, p=0.9467), medians not reached; stopped for futility. Grade 3 or higher adverse events 61.9 against 38.1 percent and rash 25.1 against 9.3 percent. | |
| 3 | Active | A Phase 3, Randomized, Open-Label, Controlled Study of Cabozantinib (XL184) in Combination With Atezolizumab vs Second Novel Hormonal Therapy (NHT) in Subjects With Metastatic Castration-Resistant Prostate Cancer | - | ||
| 3 | Active | A Randomised, Double-blind, Placebo-controlled, Multicentre Phase III Study of Olaparib Plus Abiraterone Relative to Placebo Plus Abiraterone as First-line Therapy in Men With Metastatic Castration-resistant Prostate Cancer (PROpel Study) | - | ||
ARANOTE NCT04736199 | 3 | Positive | Metastatic hormone-sensitive prostate cancer: androgen deprivation with darolutamide or placebo, without docetaxel | Darolutamide plus androgen deprivation lengthened radiographic progression-free survival compared with androgen deprivation alone; approved for this use in 2025. | |
RADICALS-HD ISRCTN40814031 | 3 | Positive | Postoperative radiotherapy after radical prostatectomy with a PSA below 5 and no metastatic disease: 6 months of androgen deprivation against 24 months, given as a gonadotrophin-releasing hormone analogue, bicalutamide 150 mg daily or degarelix, with metastasis-free survival as the primary outcome | Ten-year metastasis-free survival 78.1 percent with 24 months of androgen deprivation against 71.9 percent with 6 months (hazard ratio 0.773, 95 percent confidence interval 0.612 to 0.975, p=0.029); grade 3 or higher toxicity 19 against 14 percent. | |
| 3 | Active | China ARCHES: A Multicenter, Phase 3, Randomized, Double-blind, Placebo Controlled Efficacy and Safety Study of Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Chinese Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC) | - | ||
EMBARK NCT02319837 | 3 | Positive | High-risk biochemical recurrence (PSA doubling time ≤9 months) after local therapy: enzalutamide + leuprolide, enzalutamide alone, or leuprolide alone | MFS HR 0.42 (combination). | |
TALAPRO-2 NCT03395197 | 3 | Positive | First-line mCRPC: enzalutamide + talazoparib vs enzalutamide + placebo (all-comers and HRR-mutant cohorts) | rPFS HR 0.63 (ITT); OS HR 0.80 (ITT), 0.62 (HRR-mutant). | |
| 3 | Completed | A Phase 3b Multicenter, Open-label Abiraterone Acetate Long-term Safety Study | - | ||
| 3 | - | A Multi-Center, Randomized, Assessor-Blind, Controlled Trial Comparing the Occurrence of Major Adverse Cardiovascular Events (MACEs) in Patients With Prostate Cancer and Cardiovascular Disease Receiving Degarelix (Gonadotropin-Releasing Hormone (GnRH) Receptor Antagonist) or Leuprolide (GnRH Receptor Agonist) | - | ||
ARASENS NCT02799602 | 3 | Positive | Metastatic hormone-sensitive prostate cancer: ADT + docetaxel + darolutamide vs ADT + docetaxel | OS HR 0.68. | |
IMbassador250 NCT03016312 | 3 | Negative | Metastatic castration-resistant prostate cancer that had progressed on abiraterone: atezolizumab with enzalutamide against enzalutamide alone, open-label, with overall survival as the primary endpoint | Overall survival not improved: stratified hazard ratio 1.12 (95 percent confidence interval 0.91 to 1.37, p=0.28) for atezolizumab with enzalutamide against enzalutamide alone. | |
MAGNITUDE NCT03748641 | 3 | Mixed | First-line mCRPC: abiraterone + niraparib vs abiraterone + placebo, HRR-mutant and HRR-negative cohorts | BRCA cohort rPFS HR 0.53; HRR-negative futility. | |
PROpel NCT03732820 | 3 | Positive | First-line mCRPC, all-comers: abiraterone + olaparib vs abiraterone + placebo | rPFS HR 0.66 (ITT); OS HR 0.81 (NS). | |
| 3 | Positive | A Phase III Trial of Short Term Androgen Deprivation With Pelvic Lymph Node or Prostate Bed Only Radiotherapy (SPPORT) in Prostate Cancer Patients With a Rising PSA After Radical Prostatectomy | Five-year freedom from progression after prostatectomy 70.9 percent with prostate bed radiotherapy alone, 81.3 percent with added short-term androgen deprivation and 87.4 percent with pelvic nodal radiotherapy as well. | ||
| 3 | Completed | A Phase III Prospective Randomized Trial of Dose-Escalated Radiotherapy With or Without Short-Term Androgen Deprivation Therapy for Patients With Intermediate-Risk Prostate Cancer | - | ||
| 3 | Active | A Phase 3 Randomized, Placebo-controlled Double-blind Study of JNJ-56021927 in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone in Subjects With Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer (mCRPC) | - | ||
PEACE-1 NCT01957436 | 3 | Positive | De novo metastatic hormone-sensitive prostate cancer: ADT + docetaxel ± abiraterone ± prostate radiotherapy (2×2 factorial) | OS HR 0.82 in the overall population and HR 0.75 in the ADT plus docetaxel population; HR 0.72 in high-volume disease. | |
GETUG-AFU 17 NCT00667069 | 3 | Mixed | pT3a, pT3b or pT4a prostate cancer with positive surgical margins after radical prostatectomy: immediate adjuvant radiotherapy against delayed salvage radiotherapy at biochemical relapse, both with 6 months of triptorelin, with event-free survival as the primary endpoint | Five-year event-free survival 92 percent with adjuvant against 90 percent with salvage radiotherapy (hazard ratio 0.81, 95 percent confidence interval 0.48 to 1.36); late grade 2 or worse genitourinary toxicity 27 against 7 percent and erectile dysfunction 28 against 8 percent. | |
HERO NCT03085095 | 3 | Positive | Advanced prostate cancer needing androgen deprivation: oral relugolix 120 mg once daily against leuprolide by injection every 3 months for 48 weeks, randomised 2:1, with sustained testosterone suppression below 50 ng/dL through 48 weeks as the primary endpoint | Sustained castration through 48 weeks in 96.7 against 88.8 percent (difference 7.9 percentage points, 95 percent confidence interval 4.1 to 11.8, superior, p<0.001); castrate testosterone by day 4 in 56.0 against 0 percent; major adverse cardiovascular events 2.9 against 6.2 percent (hazard ratio 0.46, 0.24 to 0.88). | |
| 3 | Active | A Phase 3 Randomized, Placebo-controlled, Double-blind Study of Apalutamide Plus Androgen Deprivation Therapy (ADT) Versus ADT in Subjects With Metastatic Hormone-sensitive Prostate Cancer (mHSPC) | Radiographic progression-free survival at 24 months 68.2 percent with apalutamide added to androgen deprivation against 47.5 percent with placebo (hazard ratio 0.48, 95 percent confidence interval 0.39 to 0.60) and overall survival at 24 months 82.4 against 73.5 percent (0.67, 0.51 to 0.89). | ||
ARAMIS NCT02200614 | 3 | Positive | High-risk non-metastatic castration-resistant prostate cancer: darolutamide against placebo, both with continued androgen deprivation | Darolutamide lengthened metastasis-free and overall survival compared with placebo with a near-placebo side-effect profile; approved in July 2019. | |
ARCHES NCT02677896 | 3 | Positive | Metastatic hormone-sensitive prostate cancer: ADT + enzalutamide vs ADT | rPFS HR 0.39; OS HR 0.66. | |
ARMOR3-SV NCT02438007 | 3 | Negative | Metastatic castration-resistant prostate cancer with AR-V7 messenger RNA detectable in circulating tumour cells, in men naive to enzalutamide, abiraterone and chemotherapy: galeterone against enzalutamide, open-label, with radiographic progression-free survival as the primary endpoint | Closed early after 38 of a planned 148 men were randomised; AR-V7 prevalence 8 percent (95 percent confidence interval 6 to 10) among 953 prescreened men. PSA50 response 13 percent with galeterone against 42 percent with enzalutamide. Galeterone development stopped. | |
CARD NCT02485691 | 3 | Positive | Metastatic castration-resistant prostate cancer previously treated with docetaxel and with progression within 12 months on abiraterone or enzalutamide: cabazitaxel 25 mg/m2 every 3 weeks with prednisone and granulocyte colony-stimulating factor, against the other androgen receptor pathway inhibitor, with imaging-based progression-free survival as the primary endpoint | Median imaging-based progression-free survival 8.0 against 3.7 months (hazard ratio 0.54, 95 percent confidence interval 0.40 to 0.73) and overall survival 13.6 against 11.0 months (0.64, 0.46 to 0.89) for cabazitaxel against a second androgen receptor pathway inhibitor. | |
ENZAMET NCT02446405 | 3 | Positive | Metastatic hormone-sensitive prostate cancer: testosterone suppression with enzalutamide against testosterone suppression with a standard non-steroidal antiandrogen, with docetaxel allowed in both arms | Enzalutamide added to testosterone suppression improved overall survival compared with a standard non-steroidal antiandrogen. |
More receptor, or mutations (F877L, T878A) that turn antagonists into agonists.
Truncated receptor lacking the ligand-binding domain is constitutively active and invisible to enzalutamide.
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.
Which nodes have drugs →Under pressure from a drug that blocks its identity (the androgen receptor in prostate cancer, EGFR in lung cancer), a tumour can change what kind of cell it is, becoming a small-cell neuroendocrine cancer that no longer needs the blocked signal. It is the ultimate escape: not a new mutation in the engine, but a new engine.
Which nodes have drugs →KEGG's prostate cancer map centres on the androgen receptor, the hormone switch that prostate cells depend on, plus loss of PTEN and NKX3.1 that lets PI3K/AKT growth signalling run free. Hormone therapy, AR antagonists and now AKT inhibitors act on these two arms.
Which nodes have drugs →Genes are cut and pasted into messages before they are used. Blood cancers often carry mutations in the splicing machinery, and the errors create abnormal proteins that could serve as targets or immune flags.
Which nodes have drugs →Cancer cells run a few genes (MYC, their lineage factors, their fusion oncogenes) at extreme volume from giant control regions called super-enhancers. The amplifiers, BRD4, CDK7, CDK9 and Mediator, are the same in every cell, but cancers are unusually dependent on them, and that dependence is druggable.
Which nodes have drugs →No companion diagnostic in the registry measures this target.
| Cell line | Identifiers | Why it is used |
|---|---|---|
| LNCaP | CVCL_0395 | T878A; androgen-sensitive. |
| VCaP | CVCL_2235 · ACH-000115 | AR-amplified, wild-type LBD. |
| 22Rv1 | CVCL_1045 · ACH-000956 | AR-V7 expressing. |
| LAPC-4 | CVCL_4744 | Wild-type AR. |
| MDA PCa 2b | CVCL_4748 · ACH-000952 | T878A and L702H double mutant. |
| C4-2B | CVCL_4784 | Castration-resistant LNCaP derivative, bone-metastatic. |
No open questions recorded for this target yet. Suggest one.
Query for this target: (TITLE:"Androgen receptor" OR ABSTRACT:"Androgen receptor" OR TITLE:"AR" OR ABSTRACT:"AR") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Androgen receptor, not a curated reading list.
The dossier as machine-readable JSON, at /api/v1/dossiers/androgen-receptor.json: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/androgen-receptor.json. Licence CC BY-NC 4.0.