Novel Targeting of Apoptosis Pathways for Prostate Cancer Therapy
Jason B. Garrison and Natasha Kyprianou
Affiliation: Division of Urology, MS- 283, 800 Rose Street, University of Kentucky Medical Center, Lexington,KY 40536, USA.
Keywords: Apoptosis, anoikis, angiogenesis, neovascularization
Selection of treatment options for clinically localized prostate cancer is based on a host of factors including the patients age, overall health status, potential complications, clinical tumor stage and Gleason score. It is widely acknowledged that androgen independent disease remains the main obstacle to improving the survival and quality of life in patients with advanced prostate cancer. Apoptosis as a genetically regulated process has a critical endpoint that coincides with the therapeutic goal of successful treatment of androgen-dependent and androgen-independent prostate cancer. Opportunities to alter the apoptotic threshold of prostate cancer cells using antisense technology and gene therapy certainly exist, but the scope and extent of their applicability and action depends upon research delineating the many subtleties within the apoptotic pathway. Most epithelial and endothelial cells undergo apoptosis when they loose contact with the extracellular matrix (ECM), via the phenomenon of anoikis. Signaling interaction between growth factor apoptosis-signaling pathways and cellular effectors of anoikis potential and tumor vascularity provides a new molecular basis for optimizing combination approaches for the effective treatment of advanced prostate cancer. Agents that induce epithelial or endothelial cell apoptosis by antagonizing integrin binding are considered for cancer therapy via their ability to inhibit tumor vascularization. This review summarizes the current knowledge of the therapeutic benefit of apoptosis induction within the context of tumor neovascularization inhibition, and provides an insight into the consequences of anoikis induction (by different agents) in targeting angiogenesis in prostate cancer cells.
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