Grant: Project Grant

Prostate cancer (PCa) is generally dependent on the male sex hormone (androgen) for survival and progression; therefore, the primary treatment strategy for advanced and metastatic PCa is androgen deprivation therapy. However, despite an initial response, the vast majority of PCa relapse in a highly aggressive form. The most aggressive subtype, accounting for up to one-fifth of late-stage PCa, is treatment-resistant neuroendocrine PCa (NEPC). Unfortunately, there are few treatment options available for NEPC. New therapeutic targets and more effective treatments are urgently needed. In view of this, we developed a first-in-field model of NEPC that gave us a unique opportunity to study how NEPC progresses. Our findings from the model suggest that NEPC can develop from typical PCa via a transition process. In our recent study, we identified PRDM16 as a key protein regulating this transition. In this proposed study, we will explore how PRDM16 regulates the transition process during NEPC development, either on its own or in conjunction with other proteins that facilitate NEPC progression. This study will expand our understanding of how PCa transforms into more aggressive NEPC and establish a foundation for developing more effective therapies to improve the treatment of PCa patients.