Targeted therapy for advanced renal cell cancer: Cytokines and beyond

For the past 20 years cytokines have been the mainstay of treatment for advanced renal cell cancer (RCC), despite low response rates achieved and the high toxicity profile observed. The recent advances in molecular biology and the greater understanding of the von Hippel-Lindau (VHL) hypoxia-inducible factor (HIF)-hypoxia-induced gene pathway have paved the way for a plethora of novel agents that selectively inhibit key molecular events which allow the malignant process to continue. The high specificity of targeted agents should allow sparing of healthy cells thereby making them less toxic and well tolerated. However, new and unanticipated toxicities have been described with virtually all new agents, some of which may even be of a similar magnitude to cytokine therapy. Although several agents have demonstrated promising results in clinical trials, especially in terms of disease stabilization, and achieved clinical licences, issues of optimal administration regimens as well as the possible synergy when combined together are currently being explored. In this new era, IL-2 may still have a relevant role in selected subgroups of patients as well in combination with novel agents. Our review describes thoroughly the existing targeted therapies for RCC, presenting the recent clinical data and discussing the perspectives.