Androgen receptor
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).
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · The hormone switch that drives prostate cancer, attacked by castration and by pills that block the receptor.
- 1 · What it is
The hormone switch that drives prostate cancer, attacked by castration and by pills that block the receptor.
- 2 · What goes wrong in cancer
Nuclear receptor; amplification, splice variants (AR-V7), and ligand-binding-domain mutations drive resistance.
- 3 · How drugs use it
9 products aim at Androgen receptor: small molecules 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.
Biology
Nuclear receptor; amplification, splice variants (AR-V7), and ligand-binding-domain mutations drive resistance.
- Prostate cancer
- LAR-subtype TNBC
- Salivary duct carcinoma
How common it is, by cancer
| 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.
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.
The old antiandrogen pill used to block the testosterone flare from GnRH agonists and in combined androgen blockade; superseded by enzalutamide-class drugs.
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.
The most widely used androgen-receptor blocker, approved across every stage of advanced prostate cancer, including rising PSA after surgery.
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.
Men diagnosed with prostate cancer that has already spread, or that is locally advanced and high risk, should start abiraterone (or another androgen-receptor pathway inhibitor) at the same time as testosterone suppression rather than waiting for resistance. This roughly halves the risk of death over several years. The same platform later showed that docetaxel chemotherapy and, in high-volume metastatic disease, triple therapy also help, and that abiraterone benefits men with high-risk disease treated with radiotherapy.
Instead of blocking a cancer protein, a drug can now remove it entirely, which works even for proteins without a druggable active site and can overcome resistance driven by target overexpression or mutation. Several degraders are in late-stage trials for breast and prostate cancer.
Latest papers
topQuery 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.
Pages like this
not linked directly; found by shared links- TargetEstrogen receptor (ERα)
Shares Agonist and antagonist, The first PROTAC: a chimeric molecule that tags a protein for destruction, Receptor, Hormone therapy and the tag hormonal.
- TermCastration-resistant prostate cancer (CRPC)
Shares AR-V7 splice variant, Androgen receptor pathway inhibitor (ARPI), Leuprolide (leuprorelin) and GnRH agonists, Prostate Cancer Foundation (PCF).
- TermAndrogen deprivation therapy (ADT)
Shares Degarelix, Androgen receptor pathway inhibitor (ARPI), Leuprolide (leuprorelin) and GnRH agonists, mCRPC and mHSPC (castration-resistant vs hormone-sensitive prostate cancer).
- TrialLATITUDE
Shares Androgen receptor pathway inhibitor (ARPI), Karim Fizazi, mCRPC and mHSPC (castration-resistant vs hormone-sensitive prostate cancer), Abiraterone acetate.
- ProductVepdegestrant
Shares The first PROTAC: a chimeric molecule that tags a protein for destruction, Hormone therapy, Ubiquitin–proteasome system & protein homeostasis, Transcriptional machinery & addiction.
- InstitutionStand Up To Cancer
Shares Howard I. Scher, Charles L. Sawyers, Prostate Cancer Foundation (PCF), Prostate cancer.
- TechnologyMolecular glue discovery platforms
Shares The first PROTAC: a chimeric molecule that tags a protein for destruction, Monte Rosa Therapeutics, Ubiquitin–proteasome system & protein homeostasis, PROTACs & molecular glues (targeted protein degradation).
- TargetPSMA
Shares Rahul Aggarwal, Owen N. Witte, Prostate Cancer Foundation (PCF), Androgen receptor signalling.