Here, we developed novel tumor models for acquired resistance to anti-VEGF therapy by expressing a fusion protein of the mouse VEGFR2 extracellular domain and human IgG4 fragment crystallizable (Fc) region (VEGFR2-Fc) in Renca mouse renal cell carcinoma and B16F10 mouse melanoma cell lines. Here, KDR is linked to renal cell carcinoma.