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Linking the genetics of 429 men with advanced prostate cancer to how long they lived showed that only one gene, RB1, predicted a worse outcome once everything else was accounted for.
Comprehensive genomic and transcriptomic analysis of 429 patients with metastatic castration-resistant prostate cancer was linked with longitudinal clinical outcomes, integrating whole-exome, transcriptome and histological analysis. For the 128 patients treated with a first-line next-generation androgen receptor signalling inhibitor, abiraterone or enzalutamide, the association of 18 recurrent DNA- and RNA-based alterations with clinical outcome was examined, including AR variant expression, AR transcriptional output and neuroendocrine expression signatures. Of these, only RB1 alteration was significantly associated with poor survival, whereas alterations in RB1, AR and TP53 were each associated with a shorter time on treatment with a receptor signalling inhibitor.
It is the most disciplined outcome analysis in this disease and its result is deflationary in a useful way: most of the alterations people quote as prognostic do not survive adjustment, and the one that does, RB1, is also the one that marks the route to neuroendocrine transformation.
Shares RB1, Androgen receptor signalling, Castration-resistant prostate cancer (CRPC), Drug resistance (primary and acquired).
Shares RB1, Androgen receptor signalling, Driver mutation, Castration-resistant prostate cancer (CRPC).
Shares Androgen receptor signalling, Lineage plasticity & neuroendocrine transformation, Castration-resistant prostate cancer (CRPC), Drug resistance (primary and acquired).
Shares Androgen receptor signalling, Driver mutation, Castration-resistant prostate cancer (CRPC), Drug resistance (primary and acquired).
Shares RB1, Androgen receptor signalling, Lineage plasticity & neuroendocrine transformation, Castration-resistant prostate cancer (CRPC).
Shares Androgen receptor signalling, Castration-resistant prostate cancer (CRPC), p53 / RB / cell-cycle checkpoint, Drug resistance (primary and acquired).
Shares RB1, Lineage plasticity & neuroendocrine transformation, Castration-resistant prostate cancer (CRPC), Androgen receptor.
Shares RB1, Lineage plasticity & neuroendocrine transformation, Castration-resistant prostate cancer (CRPC), p53 / RB / cell-cycle checkpoint.