Grant: Project Grant

Most prostate cancers survive and grow by relying on signals from the androgen receptor (AR). Treatments that target AR signaling have been successful in controlling prostate cancer. However, about 17-20% of patients' tumor eventually come back in a more aggressive form, which is called neuroendocrine prostate cancer (NEPC). This type of cancer no longer depends on AR signaling, which makes it resistant to AR-targeting treatments. Currently, standard chemotherapy is the only option available for NEPC, but its effects are short-lived. Therefore, new treatment approaches are urgently needed to improve the management of NEPC. Our research team has developed a state-of-the-art pre-clinical NEPC model that gives us unprecedented levels of accuracy in monitoring how NEPC progresses. Using this model and detailed molecular analysis, we have identified a key early stage in NEPC development that has never been reported before. Additionally, we discovered a new protein called PROX1 that plays a critical role in driving NEPC growth. In our early study, we have found the increased PROX1 expression in clinical NEPC samples and confirmed its function associated with NEPC. These results suggest that PROX1 may play an important role in NEPC development and progression. In the proposed study, we will thoroughly investigate how PROX1 affects different aspects of NEPC and explore its potential as a target for new treatments. If successful, this study will significantly enhance our understanding of NEPC and provide new insights into the precision treatment strategy for prostate cancer patients. Identification of PROX1 as a new therapeutic target in this study could lead to more effective therapy and improve the quality of life for patients with prostate cancer.