Non-clear cell renal cell carcinoma: how new biological insight may lead to new therapeutic modalities.

Treatment for patients with metastatic non-clear cell renal cancer (RCC), who constitute 25% of all RCC patients, is largely undefined and tested algorithms remain unsatisfactory. Response rates to targeted therapy are not as high as in patients with clear cell subtypes, but novel agents provide a clinically meaningful response in some individuals. The research leading to characterization of the pathways involved in clear cell renal cancer has been recognized as a role model for the development of therapies based on genetic and molecular tumor characteristics. Similar research now provides increasing insight into signal transduction in non-clear cell subtypes. This review will present and discuss the current evidence of pathways involved in the most common non-clear cell subtypes. In addition, we will review how this may lead to the development of new treatment modalities. New targets and clinical trials will be highlighted.