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A short form of the androgen receptor, missing the part that the hormone drugs grab onto, can be detected in tumour cells circulating in the blood. Not one man whose cells carried it responded to either enzalutamide or abiraterone.
Emmanuel Antonarakis, Jun Luo and colleagues at Johns Hopkins used a quantitative reverse-transcriptase polymerase chain reaction assay for the androgen receptor splice variant 7 messenger RNA in circulating tumour cells from 62 men with metastatic castration-resistant prostate cancer starting enzalutamide or abiraterone.
AR-V7 lacks the ligand-binding domain, which is exactly what both drugs target, so the prediction was mechanical and the result was categorical: 0 percent of AR-V7-positive men had a prostate-specific antigen response on either drug, against 53 percent and 68 percent of AR-V7-negative men. Every survival endpoint followed. A decade on, AR-V7 testing is available but little used, partly because a negative result does not guarantee response and partly because the alternatives the test would send a man to, taxanes and radioligand therapy, are used in the same sequence anyway.
The first predictive resistance biomarker in prostate cancer, and a mechanism rather than a correlation: a receptor with no ligand-binding domain cannot be blocked by a drug that binds the ligand-binding domain. It is also the origin of the case for androgen receptor degraders, which destroy the protein rather than blocking a site the protein no longer has.
Shares Radiographic progression-free survival (rPFS), Take high-dose testosterone to phase 3, with progression-free survival through the second line as the primary endpoint, Randomise the order of treatment, not only the drugs: a strategy platform for metastatic prostate cancer, PSA (prostate-specific antigen) and the tag prostate-evidence.
Shares Molecular determinants of resistance to antiandrogen therapy, Take high-dose testosterone to phase 3, with progression-free survival through the second line as the primary endpoint, PSA (prostate-specific antigen), Enzalutamide and the tag prostate-evidence.
Shares Destroy the truncated androgen receptor that hormone drugs cannot touch, SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer, Neuroendocrine differentiation in prostate cancer, Abiraterone acetate and the tag prostate-evidence.
Shares Molecular determinants of resistance to antiandrogen therapy, Radiographic progression-free survival (rPFS), PSA (prostate-specific antigen), Enzalutamide and the tag prostate-evidence.
Shares Molecular determinants of resistance to antiandrogen therapy, Take high-dose testosterone to phase 3, with progression-free survival through the second line as the primary endpoint, Castration-resistant prostate cancer (CRPC), Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch and the tag prostate-evidence.
Shares Radiographic progression-free survival (rPFS), PSA (prostate-specific antigen), Enzalutamide, Castration-resistant prostate cancer (CRPC) and the tag prostate-evidence.
Shares Molecular determinants of resistance to antiandrogen therapy, PSA (prostate-specific antigen), Abiraterone acetate, Castration-resistant prostate cancer (CRPC) and the tag prostate-evidence.
Shares PSA (prostate-specific antigen), Castration-resistant prostate cancer (CRPC), Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch, Acquired resistance to every therapy and the tag prostate-evidence.