Androgen receptor
The hormone switch that drives prostate cancer, attacked by castration and by pills that block the receptor. This dossier gathers the 9 products (7 approved), 11 trials, 4 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.
Biology
Nuclear receptor; amplification, splice variants (AR-V7), and ligand-binding-domain mutations drive resistance.
- Prostate cancer
- LAR-subtype TNBC
- Salivary duct carcinoma
Elsewhere: identifiers and databases
Built from HGNC, Ensembl, UniProt and ChEMBL idsHow common it is, by cancer
Full matrix →| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Prostate cancer | >95% | AR-driven at diagnosis | AR-V7 in ~20-40% of mCRPC | Wikipedia |
| Triple-negative breast cancer | 10-15% | Luminal androgen receptor subtype | Wikipedia |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Mutation hotspots and which drugs address them
| 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.
Products by modality and phase
Browse products →| Modality | Approved | Phase 3 | Withdrawn or failed |
|---|---|---|---|
| Small molecule 9 |
Trials
Evidence ranking →| Trial | Phase | Status | Setting | Result | Products |
|---|---|---|---|---|---|
| CAPItello-281 NCT04493853 | 3 | Positive | De novo metastatic hormone-sensitive prostate cancer with PTEN deficiency: abiraterone + capivasertib vs abiraterone + placebo | rPFS significantly improved (HR reported at presentation); approved 2026. | |
| 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). | |
| ARASENS NCT02799602 | 3 | Positive | Metastatic hormone-sensitive prostate cancer: ADT + docetaxel + darolutamide vs ADT + docetaxel | OS HR 0.68. | |
| 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). | |
| PEACE-1 NCT01957436 | 3 | Positive | De novo metastatic hormone-sensitive prostate cancer: ADT + docetaxel ± abiraterone ± prostate radiotherapy (2×2 factorial) | OS HR 0.82 (ITT); 0.72 high-volume. | |
| ARCHES NCT02677896 | 3 | Positive | Metastatic hormone-sensitive prostate cancer: ADT + enzalutamide vs ADT | rPFS HR 0.39; OS HR 0.66. | |
| LATITUDE NCT01715285 | 3 | Positive | High-risk de novo metastatic hormone-sensitive prostate cancer: ADT + abiraterone vs ADT | OS HR 0.66. | |
| MEVPRO-1 NCT06551324 | 3 | Recruiting | mCRPC after abiraterone: mevrometostat + enzalutamide vs physician's choice (enzalutamide or docetaxel) | ||
| STAMPEDE NCT00268476 | platform | Positive | Multi-arm multi-stage platform in hormone-naive advanced prostate cancer: docetaxel, abiraterone, radiotherapy to the prostate, and more added to ADT | Abiraterone + ADT: OS HR 0.63 in mHSPC; docetaxel + ADT: OS HR 0.78. |
Resistance routes that involve this target
Unaddressed routes →More receptor, or mutations (F877L, T878A) that turn antagonists into agonists.
- AR degraders and N-terminal-domain inhibitors (trials); PSMA radioligand therapy
Truncated receptor lacking the ligand-binding domain is constitutively active and invisible to enzalutamide.
- Taxanes retain activity; N-terminal-domain inhibitors
Pathways where it is a node
Pathway-to-drug matrix →- Androgen receptor signallingNode: Androgen receptor · 1 druggable nodes
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 → - Lineage plasticity & neuroendocrine transformationNode: Adenocarcinoma (AR / EGFR) · 5 druggable nodes
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 → - RNA splicingNode: Aberrant isoforms (AR-V7) · 1 druggable nodes
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 → - Transcriptional machinery & addictionNode: Lineage TFs (ER, AR, ASCL1) · 4 druggable nodes
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 →
Companion diagnostics and assays
Assay registry →No companion diagnostic in the registry measures this target.
Preclinical models
All models →| 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. |
- Pten conditional (PB-Cre4; Pten flox) Wang et al., Cancer Cell 2003
Open questions
All open questions →No open questions recorded for this target yet. Suggest one.
Ideas and companies
Key papers and the live literature
Preprints →- STAMPEDE: adding abiraterone to hormone therapy at diagnosis of advanced prostate cancer · New England Journal of Medicine 2017
- The first PROTAC: a chimeric molecule that tags a protein for destruction · PNAS 2001
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.
Export
The dossier as machine-readable 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 4.0.