Fig. 6
From: Emerging role of tumor cell plasticity in modifying therapeutic response
Two models describing the mechanism of lineage switching from CRPC to NEPC. a Following ARPI treatment, NEPC can originate from a small subpopulation of mutated neuroendocrine cells surrounding the primary tumor in CRPC, or derive from overgrown CSCs in CRPC, which undergo a differentiation process to acquire an AR-independent basal-like phenotype. b AR-dependent luminal epithelial cells initially undergo developmental reprogramming to neurological PCSCs, followed by differentiation into an AR-independent basal-like NEPC by ARPI-induced neuroendocrine trans-differentiation. Due to dynamic reversible cancer cell plasticity, the newly acquired NEPC can be reverted to the luminal epithelial-like CRPC by restoring TP53 and RB1, re-exposure to androgen or inhibition of EZH2 and SOX2 implicated in pluripotency networks. PCSCs prostate cancer stem cells, SOX2 SRY-box transcription factor 2, EZH2 enhancer of zeste homolog 2
