Update on targeted therapies for clear cell renal cell carcinoma

Purpose of review The article reviews the evolution of targeted therapies for clear cell renal cell carcinoma (RCC) and recent developments in the field. The vast majority of work in kidney cancer deals with clear cell RCC, which is the most common variant of this malignancy. The identification of loss of function of the von Hippel-Lindau protein as the basis for clear cell RCC, in addition to the well designed clinical trials that have ensued, provide an outstanding model for the development of mechanism-based targeted therapy in cancer. Recent findings The treatment of advanced and metastatic RCC continues to be a major challenge for uro-oncologists despite the approval of six targeted therapies over the past 5 years. This rapid growth in therapeutic options has brought much needed improvements in overall and progression-free survival, although durable complete responses are rare. However, the plurality of treatments also poses challenges in terms of selecting the best therapy for a given patient, designing trials with appropriate comparison arms and endpoints, identifying well tolerated and effective drug combinations or sequences, and determining the role of targeted therapies in the neoadjuvant and adjuvant settings. Summary Vascular endothelial growth factor and mammalian target of rapamycin-targeted therapies continue to play a critical role in the management of advanced and metastatic RCC. Ongoing research to identify novel agents continues to build upon the work done during the elucidation of the von Hippel-Lindau/ clear cell RCC pathway. It is hoped that ongoing and planned studies will enable development of therapeutic regimens that will incorporate agents with improved toxicity and better efficacy as well as defining a role for a multidisciplinary approach to the management of advanced RCC.