Amina Zoubeidi

My research program aims at uncovering how androgen receptor activity controls phenotypic plasticity, which has been associated with the clinically relevant problem of drug resistance in prostate cancer (PCa). Resistance to newly developed androgen receptor pathway inhibitors (ARPIs), rapidly emerges and patients generally die within two 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. As a critical tool in my arsenal to investigate the highly clinically relevant problem of treatment resistance to anti-androgens, I have developed a unique set of reagents and resources, including tumours and cell lines resistant to Enzalutamide, that make me highly competitive globally in this field of research. Using this model, we discovered BRN2 as a major driver of ENZ resistance and NEPC and developed small molecule inhibitors for BRN2. For translational importance, my research group has uncovered mechanisms of cell plasticity and treatment resistance, and designed combination therapies that have guided clinical trials in CRPC including therapeutic combinations of AKT inhibitors with Enz.