Molecular Engineering of Vector-Based Oncolytic and Imaging Approaches for Advanced Prostate Cancer

摘要

Hormone refractory and metastatic prostate cancer are not well understood. Better animal models, diagnostic and treatment modalities are sorely needed for these advanced stages of disease. We have coupled non- invasive optical imaging to develop metastatic prostate cancer animal models, and vector-based diagnostic and therapeutic approaches. A highly potent and prostate-specific transcriptional regulatory system (TSTA) has been utilized to restrict the expression of our adenoviral vector specifically to prostate or prostate cancer cells. In the diagnostic approach, this TSTA system will be applied to express imaging reporter gene. Alternatively, the TSTA system will be applied to regulate the expression of viral replication proteins in the therapeutic approach. In doing so, the viral amplification and cell lysis will be directed in a prostate-specific manner. To date, the progress of this project is according to the proposed plan as the feasibility and the functionality of the prostate-targeted oncolytic system was demonstrated. Interestingly, during our investigation, we have developed several metastatic human prostate tumor models. The cancer dissemination process in these models can be easily monitored by non- invasive imaging. These metastatic animal models will be the bases for us to investigate the efficacy of our diagnostic and oncolytic therapeutic viral vectors.