How far is the horizon? From current targets to future drugs in advanced renal cancer

Purpose: The proliferative control of renal cell cancer (RCC) via vascular endothelial growth factor and mammalian target of rapamycin inhibition by targeted agents has substantially improved survival rates for RCC patients with metastatic (m) disease. However, the management of mRCC remains challenging because some patients are primarily refractory to the approved targeted agents and most therapies eventually fail because of the development of an intractable drug resistance. Tumor progression is closely related to a persistent or restored proliferation via direct and indirect oncogenic signals. Although the elucidation of cancer cell proliferation in the "-omics era" has revealed an enormous number of new potential targets, a comprehensive overview of the different pathways that might serve as new drug targets has become increasingly complex. Methods/Results: This review highlights the well-trodden pathways in mRCC that are inhibited by targeting agents and describes innovative modes of action within these pathways that are currently not targeted but are under exploration in clinical studies. Additionally, this paper highlights as future drug targets the components of tumor metabolism that supply the tumor cells with nutrition. Conclusions: These fundamental insights into RCC proliferation as a key driver of progression are urgently needed to overcome the currently improved but still limited targeted drug success.