Neuroendocrine differentiation in prostate cancer: Implications for new treatment modalities

Objectives: This review aims to provide practising clinicians with the most recent knowledge of the biological nature of prostate cancer (PC) to facilitate investigation of new treatment modalities for patients with PC, especially the hormone-refractory state of the disease. Methods: Review of the literature using PubMed search and scientific journal publications. Results: Much progress has been made towards an understanding of the development and progression of PC, and the factors which drive the development of androgen independence. Neuroendocrine (NE) cells may provide an intriguing link between NE cell differentiation and tumour progression in PC with the genetically supported formation of androgen-independent clones which regulate the proliferation of neighbouring non-NE-phenotype cancer cells in a paracrine manner by secretion of NE products. Various NE peptides stimulate proliferation of androgen-independent PC through transactivation of the androgen receptors (AR). Therefore, cancerous epithelial cells that increase their responsiveness to NE factors or induce NE cells to release trophic factors may have a survival advantage over their siblings. Conclusion: This review shows the need to improve our understanding of the biological nature of PC, especially cancer cells of the NE phenotype and their regulatory products to develop new therapeutic protocols and trials based on NE hormones and their agonists/antagonists. (C) 2004 Elsevier B.V. All rights reserved.