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. Author manuscript; available in PMC: 2019 Nov 16.
Published in final edited form as: Nat Rev Urol. 2019 Oct 7;16(11):645–654. doi: 10.1038/s41585-019-0237-8

Fig. 6 |. Lineage plasticity in mCRPC.

Fig. 6 |

Lineage plasticity has been increasingly observed in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with androgen receptor pathway inhibitors (ARPIs) to drive prostate cancer from an adenocarcinoma histology towards a neuroendocrine prostate cancer (NEPC) phenotype. This change is associated with loss of androgen receptor (AR) expression, combined loss of RB1 and TP53, and distinct epigenetic changes. In preclinical studies, inhibition of the epigenetic regulator EZH2 has a potential role in reversing the phenotype back towards an AR+ adenocarcinoma to regain responses to enzalutamide (ENZ). adeno, adenocarcinoma; EZH2i, EZH2 inhibition; tNEPC, treatment-related NEPC.