Endocrine Abstracts

Resistance to newly developed androgen receptor pathway inhibitors (ARPIs), such as abiraterone and enzalutamide, rapidly emerges and patients generally die within 2 years. In particular, a subset of patients who relapse following ARPI therapy exhibit lineage switching whereby tumours shed their dependence on AR signaling and emerge with neuroendocrine features. These tumours, termed treatment induced neuroendocrine prostate cancer (t-NEPC), carry an extremely poor prognosis and, to date, treatment remains decades old cytotoxic chemotherapy which carries a short-lived response at the cost of significant toxicity. Thus, the need to develop targeted treatments for this devastating disease is of paramount importance. Dr Zoubeidi will discuss how cell plasticity including cancer stem cells and neuroendocrine are mechanisms of ENZ resistance that could be in part governed by changes in the epigenome and why the transcription factor BRN2 is a major regulator/driver and a promising target for t-NEPC.