Novel targeted agents have transformed the treatment of metastatic renal cell carcinoma, with significant clinical improvements compared with the previous standard of care. However, we still need to define how to use existing therapies optimally to provide maximal clinical benefit. The molecular pathways involved in the proliferation of cancer cells and tumor angiogenesis are complex. Clinical trials are currently evaluating whether therapeutic benefit can be improved by combining agents that block multiple aspects of the same or different pathways, thereby providing additive or synergistic effects. The data from combination trials to date suggest that these approaches are feasible, but all approaches tested today have been shown to be either too toxic, or currently not more active than monotherapy (may be with the exception of bevacizumab-interferon combination. This strongly suggests that combining drugs with completely different mechanisms of action. In this regards, combining VEGF-targeted therapies with new targeted immunotherapy such as ipilimumab or anti-PD 1 or PD-L1 antibodies might be the future for combination therapy in renal cell carcinoma.
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