Figure 1. Signaling pathways inhibition by targeted agents in mRCC.

RCC is a highly vascularized tumor type. The chronic angiogenesis is required for growth of these tumors. Under normal conditions HIF (hypoxia inducible factor) is constitutively degraded. HIF promotes transcription of gene involved in the angiogenesis-pathway and tumor progression such as VEGF, PDGF and TGF-alfa. Inactivation of the von Hippel-Lindau (VHL) gene leads to accumulation of HIF transcription factors and subsequent activation of several mediator of angiogenesis. Also the activation of the mammalian target of rapamycin (mTOR) signaling pathway may result in HIF accumulation. Temsirolimus and everolimus are kinase inhibitors of mTOR complex 1 (mTORC1); bevacizumab is a humanized anti-VEGF monoclonal antibody; sorafenib, sunitinib, pazopanib and axitinib are multikinase inhibitor (TKIs) of growth factor receptors involved in the activation of angiogenesis-related pathways.