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Over two decades a new kind of advanced prostate cancer appeared that uses neither the androgen receptor nor a neuroendocrine programme, and it runs on a growth factor pathway instead.
Androgen receptor signalling is the distinctive feature of prostate carcinoma and the major therapeutic target in metastatic disease, but androgen receptor antagonism can produce tumours that bypass a functional requirement for the receptor, often through neuroendocrine transdifferentiation. Through molecular assessment of metastatic prostate cancers over two decades, a phenotypic shift was found with the emergence of an androgen receptor-null, neuroendocrine-null phenotype. These double-negative prostate cancers showed elevated FGF and MAPK pathway activity, which can bypass androgen receptor dependence, and pharmacological inhibitors of MAPK or FGFR repressed their growth in vitro and in vivo.
It shows that leaving androgen receptor dependence does not have to mean becoming neuroendocrine, and it names a treatable pathway for a group of men whose tumours would otherwise be described only by what they lack.
Shares Histologic transformation, Neuroendocrine and small-cell prostate cancer, Lineage plasticity & neuroendocrine transformation, Androgen receptor signalling.
Shares Cancer Cell, Androgen receptor signalling, Resistance routes: how a blocked pathway comes back, Castration-resistant prostate cancer (CRPC).
Shares Histologic transformation, Neuroendocrine and small-cell prostate cancer, Lineage plasticity & neuroendocrine transformation, Castration-resistant prostate cancer (CRPC).
Shares Histologic transformation, Neuroendocrine and small-cell prostate cancer, Lineage plasticity & neuroendocrine transformation, Androgen receptor signalling.
Shares Androgen receptor signalling, Resistance routes: how a blocked pathway comes back, Castration-resistant prostate cancer (CRPC), Drug resistance (primary and acquired).
Shares Lineage plasticity & neuroendocrine transformation, Androgen receptor signalling, Castration-resistant prostate cancer (CRPC), Drug resistance (primary and acquired).
Shares Androgen receptor signalling, Resistance routes: how a blocked pathway comes back, Castration-resistant prostate cancer (CRPC), Drug resistance (primary and acquired).
Shares Histologic transformation, Neuroendocrine and small-cell prostate cancer, Lineage plasticity & neuroendocrine transformation, Androgen receptor.