Neuroendocrine differentiation (ND) is widely observed in prostate cancer (PC). Its role in clinical practice is controversial, but preclinical and clinical evidences underline the association of ND with poor prognosis in PC patients. Neuroendocrine (NE) cells could condition the PC progression, mainly stimulating the PC exocrine neoplastic cells proliferation through the production of paracrine growth factors. Thus, the castrated adapted neoplastic cells are favored to outgrowth through an androgen receptor independent mechanism. Moreover proportion of NE cells in PC increases because of tumor treatment, mainly androgen deprivation therapy, enormously amplifying the promotion of the PC exocrine component growth stimulated by neuroendocrine paracrine growth factors. This chapter provides an overview of the most relevant clinical studies demonstrating a significant correlation between ND and PC behavior, indicating that ND could represent a prognostic parameter in PC, and strongly suggesting that NE cells in a castrate resistant patients could be targeted through specific treatment.
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