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The hormone switch that drives prostate cancer, attacked by castration and by pills that block the receptor.
Androgen deprivation plus AR pathway inhibitors (abiraterone, enzalutamide, apalutamide, darolutamide) is standard in advanced prostate cancer. AR degraders, AR N-terminal domain inhibitors, and combinations with PARP or AKT inhibitors address castration resistance. AR is also a target in a subset of TNBC (luminal androgen receptor subtype).
In plain words · The hormone switch that drives prostate cancer, attacked by castration and by pills that block the receptor.
The hormone switch that drives prostate cancer, attacked by castration and by pills that block the receptor.
Nuclear receptor; amplification, splice variants (AR-V7), and ligand-binding-domain mutations drive resistance.
19 products aim at Androgen receptor: small molecules, degraders and hormonal therapies. Drugs cut off the hormone supply, block the receptor so the hormone cannot bind, or send the receptor to the cell's waste disposal.
Tumour-associated overexpression: HPA finds the RNA cancer enhanced in cancer (Breast Invasive Carcinoma (TCGA), Prostate Adenocarcinoma (TCGA)) and tissue enhanced in normal liver, so the tumour and the normal tissue it comes from share the target and the medicine relies on the difference in level. HPA AR: RNA tissue enhanced (liver 36 nTPM); high antibody staining in 2 normal tissues; highest cancer staining prostate cancer (7 of 8 high). Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Prostate cancer, Breast cancer (all types)); approvals of single-target medicines aimed at it also list Salivary gland cancers, not counted; Open Targets associates it with 5 specific cancer types at or above 0.5 (prostate cancer, prostate carcinoma, prostate adenocarcinoma, Familial prostate cancer, breast cancer). (Rule 7 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas AR tissue; Human Protein Atlas AR pathology; Open Targets ENSG00000169083 associations
First described 1988. Earliest sequence paper UniProt cites for the protein: Lubahn D.B. et al, Mol. Endocrinol, 1988, "The human androgen receptor: complementary deoxyribonucleic acid cloning, sequence analysis and gene expression in prostate". Source.
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
Cell lines and mouse models for this target →
Nuclear receptor; amplification, splice variants (AR-V7), and ligand-binding-domain mutations drive resistance.
RNA: tissue enhanced (liver 36 nTPM), detected in many normal tissues.
Medium: Breast, Endometrium, Fallopian tube, Kidney, Testis.
RNA cancer enhanced: Breast Invasive Carcinoma 25 pTPM, Prostate Adenocarcinoma 22 pTPM.
Medium only: endometrial cancer, head and neck cancer, lung cancer.
HPA AR tissue · HPA AR pathology · HPA protein class: FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| 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.
Abiraterone is a pill that shuts down testosterone production everywhere, including inside the tumour. Discovered at the Institute of Cancer Research, now generic and used from the first metastatic diagnosis.
An AR blocker approved for prostate cancer that has spread and for high-risk disease before it shows on scans.
AZD9750 is an experimental protein degrader from AstraZeneca in phase 2 trials for prostate cancer, aimed at Androgen receptor.
The old antiandrogen pill used to block the testosterone flare from GnRH agonists and in combined androgen blockade; superseded by enzalutamide-class drugs.
BMS-986365 is an experimental protein degrader from Celgene in phase 3 trials for prostate cancer, aimed at Androgen receptor.
Darolutamide is an AR blocker that barely enters the brain, so it causes fewer falls and cognitive side effects; it is approved with and without chemotherapy.
An injectable hormone blocker for prostate cancer that lowers testosterone within days without the initial surge caused by agonists.
Enzalutamide is a second-generation androgen-receptor blocker that stops the receptor binding testosterone, entering the nucleus and switching on genes. It is approved at every stage of advanced prostate cancer, from rising PSA after surgery to castration-resistant disease, and fatigue, falls and memory problems are its main drawbacks.
EP0062 is an experimental small-molecule drug from Ellipses Pharma in phase 2 trials for HR-positive / HER2-negative breast cancer, aimed at Androgen receptor.
Fluoxymesterone is an oral male hormone approved in 1956 and once used to palliate advanced breast cancer in women, an approach abandoned when better tolerated antioestrogens and aromatase inhibitors arrived.
Flutamide was the first tablet to block testosterone at the prostate cancer cell. It is taken with an injection that stops testosterone production, but newer drugs have largely replaced it.
An experimental prostate cancer tablet meant to work in men whose cancer makes a broken form of the androgen receptor. The trial designed to prove it collapsed.
Leuprolide is the injectable that shuts off testosterone production, the foundation of hormone therapy for prostate cancer since the 1980s; it is also used for ovarian suppression in premenopausal breast cancer.
A drug designed to block the part of the androgen receptor that resistant variants keep; its phase 2 was stopped for futility and development ended.
An epigenetic drug that may re-sensitise prostate cancer to hormone therapy, in three phase 3 trials with enzalutamide.
Nilutamide (Nilandron) is an older antiandrogen tablet started on the day of surgical castration for metastatic prostate cancer; it is rarely used now because of lung and eye side effects.
QLH12016 is an experimental protein degrader from Qilu Pharmaceutical in phase 2 trials for prostate cancer, aimed at Androgen receptor.
Rezvilutamide is Hengrui's androgen receptor blocker, approved in China in 2022 for high-volume metastatic hormone-sensitive prostate cancer on the CHART trial, where it improved survival over bicalutamide.
Triptorelin (Trelstar) is a one-, three- or six-monthly injection that switches off testosterone production for men with advanced prostate cancer.
The 48 most recent of 49 papers; see them all →
It is the right shape of answer for a transition that is epigenetic rather than genetic, and it could in principle spare the biopsy that is currently the only way to make this diagnosis.
It separates two explanations that are usually run together. Some of the difference in prostate cancer outcomes by race is in the tumour genome and persists when access to the same centre is held constant, and some of it tracks with income rather than with ancestry, so equalising access alone would not eliminate the gap.
It established plasma profiling as a routine alternative to tissue for the BRCA question in advanced prostate cancer, with a sensible rule attached: if plasma finds nothing actionable, go back to tissue. It also documents at scale both the extra resistance information plasma gives and the clonal haematopoiesis noise that comes with it.
It is the prospective test of the PI3K and androgen receptor feedback hypothesis in men, and it shows both halves of the answer: the biomarker-selected population benefits, and the benefit is small enough that the toxicity has to be weighed honestly.
The first randomised evidence that the order in which prostate cancer treatments are given changes how long they work, independently of which treatments they are. It is also a rare trial in which quality of life pointed one way and the primary endpoint pointed nowhere.
It splits the alterations into two groups with different practical meanings. The repair defects are present at diagnosis at close to their castration-resistant prevalence, so testing early is worthwhile; AR, TP53 and RB1 changes accumulate later, so a diagnostic sample does not answer questions about the disease in front of you at relapse.
It fills the gap between the primary-tumour atlases and the castration-resistant series by describing the disease at the moment most treatment decisions are actually made, and it identifies SPOP as a favourable marker rather than a neutral one.
The FUSCC cohort is the East Asian reference and the basis of the FUTURE subtype-guided umbrella trial; its LAR findings point to CDK4/6 and HER2-mutant strategies rather than PARP inhibitors for that subtype.
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.
Shares Agonist and antagonist, The first PROTAC: a chimeric molecule that tags a protein for destruction, Receptor, Chemical carcinogenesis - receptor activation and the tag hormonal.
Shares Galeterone, Proposed morphologic classification of prostate cancer with neuroendocrine differentiation, Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer, Nuclear-localised androgen receptor splice variant 7 in circulating tumour cells as a predictive biomarker in castration-resistant prostate cancer.
Shares BMS-986365, Galeterone, Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer, Nuclear-localised androgen receptor splice variant 7 in circulating tumour cells as a predictive biomarker in castration-resistant prostate cancer.
Shares Genomic correlates of clinical outcome in advanced prostate cancer, Substantial interindividual and limited intraindividual genomic diversity among tumours from men with metastatic prostate cancer, Unravelling triple-negative breast cancer molecular heterogeneity using an integrative multiomic analysis, Combined tumour suppressor defects characterise clinically defined aggressive variant prostate cancers.
Shares Huggins and Hodges 1941: the effect of castration, of oestrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate, Destroy the truncated androgen receptor that hormone drugs cannot touch, Abiraterone in metastatic prostate cancer without previous chemotherapy, The evolutionary history of lethal metastatic prostate cancer.
Shares Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer, Nuclear-localised androgen receptor splice variant 7 in circulating tumour cells as a predictive biomarker in castration-resistant prostate cancer, Genomic correlates of clinical outcome in advanced prostate cancer, Molecular profiling stratifies diverse phenotypes of treatment-refractory metastatic castration-resistant prostate cancer.
Shares Proposed morphologic classification of prostate cancer with neuroendocrine differentiation, Detecting neuroendocrine prostate cancer through tissue-informed cell-free DNA methylation analysis, Mevrometostat, Molecular profiling stratifies diverse phenotypes of treatment-refractory metastatic castration-resistant prostate cancer.
Shares Differences in prostate cancer genomes by self-reported race, IPATential150: ipatasertib plus abiraterone and prednisolone in metastatic castration-resistant prostate cancer, Reciprocal feedback regulation of PI3K and androgen receptor signalling in PTEN-deficient prostate cancer, IMbassador250.