Molecular targeted therapy in advanced renal cell carcinoma: A review of its recent past and a glimpse into the near future

Renal cell carcinoma (RCC) is the most lethal of all urologic malignancies. Recent translational research in RCC has led to the discovery of a new class of therapeutics that specifically target important signaling molecules critical in the pathogenesis of the disease. It is now clear that these new molecular targeted agents have revolutionized the management of patients with metastatic RCC. However, the exact molecular mechanism accounting for their clinical effect is largely unknown and a significant proportion of patients with metastatic RCC do not respond to these therapeutics. This review presents the relevant background leading to the development of molecular targeted therapy for patients with advanced RCC and summarizes current management issues in particular relating to the emerging problem of treatment resistance and the need for clinical and laboratory biomarkers to predict treatment outcomes in these patients. In addition, this paper will also address surgical issues in the era of molecular targeted therapy including the role of cytoreductive surgery and surgical safety issues post-molecular therapy. Lastly, this review will also address the need to explore new molecular treatment targets in RCC and briefly present our work on one of the promising molecular targets - the type 1 insulin-like growth factor receptor (IGF1R), which may in the near future lead to the development of anti-IGF1R therapy for patients with advanced RCC.