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Sequencing showed that neuroendocrine prostate cancer arises from the same cells as ordinary prostate adenocarcinoma but diverges through loss of RB1 and TP53 and changes in DNA methylation rather than new mutations, explaining how the cancer escapes hormone therapy by changing identity.
Whole-exome and methylation analysis of 114 metastatic biopsies from patients with castration-resistant prostate cancer, comparing adenocarcinoma with neuroendocrine prostate cancer.
Neuroendocrine tumours shared clonal origin with adenocarcinoma, showed frequent RB1 loss and TP53 mutation, low androgen receptor signalling, distinct epigenetic profiles and overexpression of EZH2, with a lineage-switch rather than a distinct mutational driver.
Treatment-emergent neuroendocrine prostate cancer is understood as lineage plasticity under androgen receptor blockade; EZH2, DLL3 and Aurora kinase are the targets under investigation.
Shares SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer, Treatment-emergent neuroendocrine transformation (recognising it), Watch for the cancer changing cell type before the biopsy says neuroendocrine, and act on it, Histologic transformation.
Shares Treatment-emergent neuroendocrine transformation (recognising it), Histologic transformation, Neuroendocrine and small-cell prostate cancer, Lineage plasticity & neuroendocrine transformation.
Shares Treatment-emergent neuroendocrine transformation (recognising it), Histologic transformation, Neuroendocrine and small-cell prostate cancer, Lineage plasticity & neuroendocrine transformation.
Shares Treatment-emergent neuroendocrine transformation (recognising it), Histologic transformation, Neuroendocrine and small-cell prostate cancer, RB1.
Shares Neuroendocrine differentiation in prostate cancer, SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer, Watch for the cancer changing cell type before the biopsy says neuroendocrine, and act on it, Neuroendocrine and small-cell prostate cancer.
Shares RB1, Nature Medicine, Clonal evolution & minimal residual disease, Castration-resistant prostate cancer (CRPC).
Shares RB1, Lineage plasticity & neuroendocrine transformation, Castration-resistant prostate cancer (CRPC), Androgen receptor.
Shares Histologic transformation, Neuroendocrine and small-cell prostate cancer, Lineage plasticity & neuroendocrine transformation, Castration-resistant prostate cancer (CRPC).