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A change in the part of the androgen receptor that hormone drugs attach to. Depending on which change it is, another hormone the man is already taking can switch the receptor on, or the blocking drug can start behaving as an activating one.
Androgen receptor mutations in this domain were first described in metastatic androgen-independent prostate cancer, where 5 of 10 men carried one and two of the mutant receptors could be activated by progesterone and by oestrogen in transfected cells (Taplin 1995). They are almost entirely a property of treated disease: cBioPortal records AR mutation in 61 of 444 samples (13.7%) in prad_su2c_2019 and 27 of 150 (18.0%) in prad_su2c_2015, against 2 of 494 (0.4%) in the TCGA primary cohort, where neither record falls in the ligand-binding domain at all. The spectrum is narrow and it tracks the treatment. In prad_su2c_2019 (72 mutation records): L702H 17, T878A 15, H875Y 11, W742C 8, W742L 4, F877L 3. L702H makes the receptor responsive to glucocorticoid, which matters because abiraterone is given with prednisone or prednisolone; T878A and H875Y open the pocket to progestogens and older antiandrogens; F877L converts enzalutamide and apalutamide from antagonists into agonists. Plasma detects compound and polyclonal combinations that a single biopsy cannot (Tukachinsky 2021).
In plain words · The hormone switch that drives prostate cancer, attacked by castration and by pills that block the receptor.
A report that says only that the androgen receptor is mutated has not answered the question. Which change it is decides whether a different hormone tablet is still worth trying, and whether a steroid being taken alongside could be feeding the cancer. It is a question for a specialist centre, because no approval depends on it.
Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.
A missense substitution in the AR ligand-binding domain on tumour or plasma sequencing, reported by specific residue rather than as AR mutated, since the clinical meaning differs by allele and more than one allele is often present at once.
“Point mutations in the androgen-receptor gene were identified in metastatic cells from 5 of the 10 patients examined... Functional studies of two of the mutant androgen receptors demonstrated that they could be activated by progesterone and estrogen.”
Taplin et al., New England Journal of Medicine 1995No approval uses this readout as a threshold. It is defined by Taplin et al., N Engl J Med 1995: mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer.
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.
The design specification for the second-generation antiandrogens. A drug for castration-resistant prostate cancer has to stay an antagonist when the receptor is abundant, which is what enzalutamide, apalutamide and darolutamide were engineered to do and what bicalutamide fails to do.
It established that the receptor in resistant prostate cancer is not silent but promiscuous, which is why the specific allele matters clinically: a receptor that will accept a glucocorticoid or a progestogen changes what should and should not be prescribed alongside the hormonal agent.
Shares AR-V7 splice variant, AR amplification (gene and upstream enhancer), Androgen receptor signalling, Castration-resistant prostate cancer (CRPC) and the tags biomarker, resistance.
Shares Cross-resistance, Resistance routes: how a blocked pathway comes back, Drug resistance (primary and acquired), Comprehensive genomic profiling and the tags biomarker, resistance.
Shares Resistance routes: how a blocked pathway comes back, Drug resistance (primary and acquired), Circulating tumour DNA (ctDNA), Comprehensive genomic profiling and the tags biomarker, resistance.
Shares Genomic analysis of circulating tumour DNA in 3,334 patients with advanced prostate cancer identifies targetable BRCA alterations and AR resistance mechanisms, AR amplification (gene and upstream enhancer), Androgen receptor, Circulating tumour DNA (ctDNA) and the tag biomarker.
Shares Circulating tumour DNA (ctDNA) and the tags biomarker, resistance.
Shares the tags biomarker, resistance.
Shares the tags biomarker, resistance.
Shares AR-V7 splice variant, Androgen receptor signalling, Resistance routes: how a blocked pathway comes back, Castration-resistant prostate cancer (CRPC).