Figure 2.

The diverse factors (cellular, molecular and therapeutic) involved in mediating neuroendocrine differentiation (NED) in PCa. Various factors that affect PCa cells include androgen deprivation-, radio- and chemo-therapy. In addition, the cells of tumor microenvironment (TME) including mast cells, cancer associated fibroblasts (CAFs), macrophages and bone marrow stromal cells (BMSCs) have been shown to promote the NED. Furthermore, calcium ion channels and alteration in calcium ion homeostasis play crucial roles in drug resistance and NED. In addition, Exosomes secreted from PCa cells have also been associated with NED. A few examples of molecular pathways are represented.