Prostate cancer (PCa) is one of the most frequent types of cancer and a leading cause of cancer-related death among males worldwide. Androgen deprivation therapy (ADT) has generated impressive effects in treating advanced PCa. However, even with the application of potent second-generation antiandrogen agents including enzalutamide and abiraterone, the most majority of PCa patients suffer from disease relapse inevitably. New treatment options or novel combination therapies in addition to ADT are urgently needed for advanced PCa. Lineage plasticity is often exploited by cancer cells to acquire therapeutic resistance. Lineage transition from adenocarcinoma (AD) to aggressive neuroendocrine (NE) derivatives is a common type of cancer cell plasticity in ADT-treated prostate adenocarcinoma (ADPC). Treatment-induced neuroendocrine prostate cancer (NEPC), which display small cell-like carcinoma features and increased expression of neuronal markers, such as synaptophysin (SYP), chromogranin A (CHGA), and neuron-specific enolase (NSE), are highly aggressive and lack effective clinical interventions. Other than NEPC, double negative prostate cancer (DNPC) with a low or negative expression of AR and NE markers, is an emerging CRPC subtype following application of potent AR antagonists. It is reported that DNPC account for proximately 21% of CRPC based on necropsies of 30 patients from a CRPC cohort study performed at University of Washington. Therefore, delineating the molecular mechanism by which cancer cells acquire enhanced cell lineage plasticity and identifying actionable drug targets would benefit the development of novel therapeutic strategies for the AR-/LOW prostate cancers.
Prof. He Zhu
School of Medicine, SJTU