Targeting Key Players of Neuroendocrine Differentiation in Prostate Cancer

Abstract

Neuroendocrine prostate cancer (NEPC) is a highly aggressive subtype of prostate cancer (PC) that commonly emerges through a transdifferentiation process from prostate adenocarcinoma and evades conventional therapies. Extensive molecular research has revealed factors that drive lineage plasticity, uncovering novel therapeutic targets to be explored. A diverse array of targeting agents is currently under evaluation in pre-clinical and clinical studies with promising results in suppressing or reversing the neuroendocrine phenotype and inhibiting tumor growth and metastasis. This new knowledge has the potential to contribute to the development of novel therapeutic approaches that may enhance the clinical management and prognosis of this lethal disease. In the present review, we discuss molecular players involved in the neuroendocrine phenotype, and we explore therapeutic strategies that are currently under investigation for NEPC.

Keywords: lineage plasticity; neuroendocrine transdifferentiation; prostate cancer; targeted therapy.

Figure 1

Molecular events and key factors contributing to NEPC transdifferentiation from prostate adenocarcinoma. DDR: DNA damage response, EMT: epithelial-to-mesenchymal transition, MIF: macrophage migration inhibitory factor.