Hu Chang-Deng, Choo Richard, Huang Jiaoti
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University Center for Cancer Research, Purdue University , West Lafayette, IN , USA.
Department of Radiation Oncology, Mayo Clinic , Rochester, MN , USA.
Front Oncol. 2015 Apr 14;5:90. doi: 10.3389/fonc.2015.00090. eCollection 2015.
Neuroendocrine differentiation (NED) in prostate cancer is a well-recognized phenotypic change by which prostate cancer cells transdifferentiate into neuroendocrine-like (NE-like) cells. NE-like cells lack the expression of androgen receptor and prostate specific antigen, and are resistant to treatments. In addition, NE-like cells secrete peptide hormones and growth factors to support the growth of surrounding tumor cells in a paracrine manner. Accumulated evidence has suggested that NED is associated with disease progression and poor prognosis. The importance of NED in prostate cancer progression and therapeutic response is further supported by the fact that therapeutic agents, including androgen-deprivation therapy, chemotherapeutic agents, and radiotherapy, also induce NED. We will review the work supporting the overall hypothesis that therapy-induced NED is a mechanism of resistance to treatments, as well as discuss the relationship between therapy-induced NED and therapy-induced senescence, epithelial-to-mesenchymal transition, and cancer stem cells. Furthermore, we will use radiation-induced NED as a model to explore several NED-based targeting strategies for development of novel therapeutics. Finally, we propose future studies that will specifically address therapy-induced NED in the hope that a better treatment regimen for prostate cancer can be developed.
前列腺癌中的神经内分泌分化（NED）是一种公认的表型变化，通过这种变化，前列腺癌细胞转分化为神经内分泌样（NE样）细胞。NE样细胞缺乏雄激素受体和前列腺特异性抗原的表达，并且对治疗具有抗性。此外，NE样细胞以旁分泌方式分泌肽类激素和生长因子，以支持周围肿瘤细胞的生长。越来越多的证据表明，NED与疾病进展和不良预后相关。治疗药物，包括雄激素剥夺疗法、化疗药物和放疗，也会诱导NED，这一事实进一步支持了NED在前列腺癌进展和治疗反应中的重要性。我们将回顾支持以下总体假设的研究工作，即治疗诱导的NED是一种治疗抗性机制，并讨论治疗诱导的NED与治疗诱导的衰老、上皮-间质转化和癌症干细胞之间的关系。此外，我们将以辐射诱导的NED为模型，探索几种基于NED的靶向策略，以开发新型治疗方法。最后，我们提出未来的研究，将专门针对治疗诱导的NED，希望能够开发出更好的前列腺癌治疗方案。
