Editorial [Hot topic: Prostate Cancer Therapy (Guest Editors: N. Sharifi and J.B. Aragon-Ching)]

Prostate cancer is the leading non-cutaneous cancer among American men. While most prostate cancers are diagnosed in the early stages and are potentially curable, a subset of men will experience biochemical relapse or manifest with metastatic disease. Treatment of metastatic prostate cancer continues to be an area of increased unmet need. As such, novel therapeutic agents are being developed. Up until recently, hormonal therapy has been the cornerstone of treatment for metastatic prostate cancer. Results from cytotoxic chemotherapy had been disappointing until the advent of taxane use, making docetaxel and prednisone the standard first line of treatment for metastatic castrationresistant prostate cancer today. However, limited therapy exists after disease progression from the use of taxanes. Several promising fields of investigation and agents are currently in development, including angiogenic/tyrosine kinase inhibitors, androgen receptor manipulation, immunologic/vaccine strategies, prostate cancer stem cells, bone-targeting agents, and novel cytotoxic compounds, provide interesting insights into molecular targets and rational drug design. In this issue, Lee and Aragon-Ching provide background on the use of cytotoxic chemotherapy as the foundation for treatment of metastatic castration-resistant prostate cancer, with alternative second-line chemotherapeutic agents and promising novel cytotoxics in development. Madan and Dahut provide data on the rationale for using angiogenic inhibitors and promising agents in development for targeting the prototype, vascular endothelial growth factor and other ligands. Similarly, thalidomide and its analogues have been utilized in the treatment of prostate cancer. Sissung et al. provide provocative data on the mechanism of action, metabolites, and novel analogues in preclinical and clinical development. Metastatic prostate cancer frequently involves bone. Mohammad, et al. detail the bone microenvironment, animal models of bone metastases, along with the development of bone-targeted therapies that are critical to the treatment of prostate cancer. The most expansive area of molecular targeting in oncology has been the development of a plethora of tyrosine kinase inhibitors. Limvorasak and Posadas provide a comprehensive review of preclinical and clinical evaluation of tyrosine kinase inhibitors for prostate cancer. Androgen receptor signaling also proves to be an important pathway of treating prostate cancer both in the pre- and post-chemotherapy setting, and Sharifi provides insights into the mechanisms of resistance to hormonal therapies, along with strategies and investigational agents for overcoming it. Various immunotherapeutic strategies and exciting results from mature clinical data are presented by Arlen and Gulley, with the conclusion that immunotherapy's time has finally come. A major advance in cancer biology has been the identification cancer stem cells as a minor component of the tumor but a critical subset that is resistant to chemotherapy. Crea, et al. describe the identification and biology of prostate cancer stem cells and discuss investigational agents that specifically target this important population of tumor cells. We hope that the readers of this thematic issue will find these concise reviews of relevant anti-cancer drugs in development with a special focus on cytotoxic agents, hormonal therapies, immunotherapies, antiangiogenesis agents, thalidomide analogs, bone targeting agents, kinase inhibitors and stem cell targeting agents, used in the treatment of prostate cancer, valuable and useful, for the research and treatment of men with prostate cancer.