Using molecular biology to develop drugs for renal cell carcinoma

Background: Renal cell carcinoma is a disease marked by a unique biology which has governed its long history of poor response to conventional cancer treatments. The discovery of the signaling pathway activated by inappropriate constitutive activation of the hypoxia inducible factors, transcription factors physiologically and transiently stabilized in response to low oxygen, has provided a basis to devise treatment strategies to target this oncogenic pathway. Objective: A review of the molecular pathogenesis of renal cell cancer (RCC) and molecularly targeted therapies, both those available at present and those in development, is provided. In addition, trials involving combination or sequential targeted therapy are discussed. Method: A detailed review of the literature describing the molecular biology of RCC and novel therapies was performed and summarized. Results/conclusion: Therapeutics targeting angiogenesis constitute the first class of agents that provide clinical benefit in most patients and herald renal cell carcinoma as a solid tumor paradigm for the development of novel therapeutics. Multiple strategies targeting this and other identified pathways in renal cell carcinoma provide numerous potential opportunities to make major improvements in treating this historically devastating cancer.