Figure 3. Hypothetical PCSCs in CRPC.

ADT selectively targets AR⁺ PCa cells and has been shown to enrich AR⁻ PCa cells, which may result from preferential elimination by ADT of AR⁺ cells as well as de-differentiation of AR⁺ PCa cells to AR⁻ cells (top). Clinical CRPCs contain distinct AR⁺ and AR⁻ clones, both of which might contain their own CSCs. In AR⁺ clones, PCSCs could have AR amplification or ligand-independent AR signaling pathways to support the self-renewal in androgen deprived environment. Several potential CSC subpopulations in AR⁻ and AR⁺ PCa cell clones are indicated.