KDR and neoplasm: The possible mechanisms of resistance to the antiangiogenic treatment of RCC are as follows: (1) upregulation of angiogenic factor expression [49], (2) changes in the tumor microenvironment [50], (3) the reversible transformation of epithelial cells into mesenchymal cells [51], (4) alternate upregulation of antivascular signaling pathways [52], and (5) alternation of VEGFR ligands [53].