Androgen receptor signalling
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.
Testicular testosterone (and adrenal precursors converted intratumourally via CYP17A1) is reduced to DHT by 5α-reductase and binds AR, which translocates to the nucleus and drives PSA, TMPRSS2-ERG, and proliferation genes. GnRH agonists/antagonists shut testicular production; abiraterone blocks CYP17A1; enzalutamide, apalutamide, darolutamide block AR. Castration resistance arises via AR amplification, ligand-binding mutations, splice variants (AR-V7 lacks the ligand domain), glucocorticoid receptor substitution, and lineage plasticity to neuroendocrine phenotype.
In one picture
Same key-and-lock idea as oestrogen: castration stops making keys, abiraterone shuts the tumour's own key factory, enzalutamide blocks the lock. AR-V7 is a lock with no keyhole that is permanently open.
Diagram
top- GnRH agonists/antagonists (leuprolide, relugolix)
- CYP17A1 inhibitor abiraterone
- AR antagonists enzalutamide, apalutamide, darolutamide
- PARP inhibitors + ARPI in HRR-mutant disease; capivasertib + abiraterone in PTEN-deficient
- AR degraders, N-terminal domain inhibitors (trials)
Pages like this
not linked directly; found by shared links- TermAndrogen receptor pathway inhibitor (ARPI)
Shares Bicalutamide, Castration-resistant prostate cancer (CRPC), Enzalutamide, Abiraterone acetate.
- CollectionProstate Cancer Foundation (PCF)
Shares Castration-resistant prostate cancer (CRPC), Enzalutamide, Abiraterone acetate, Androgen receptor.
- PersonJohann de Bono
Shares Abiraterone acetate, Androgen deprivation & AR pathway inhibitors, Androgen receptor, Olaparib.
- TrialCAPItello-281
Shares Capivasertib, AKT, Abiraterone acetate, Prostate cancer.
- TermmCRPC and mHSPC (castration-resistant vs hormone-sensitive prostate cancer)
Shares Castration-resistant prostate cancer (CRPC), Enzalutamide, Abiraterone acetate, Androgen receptor.
- PersonCharles L. Sawyers
Shares Apalutamide, Enzalutamide, Androgen receptor, Prostate cancer.
- PersonHoward I. Scher
Shares Enzalutamide, Abiraterone acetate, Androgen receptor, Prostate cancer.
- PathwayDNA damage response & homologous recombination
Shares PARP inhibitor + AR pathway inhibitor (prostate), Niraparib, Talazoparib, Olaparib.