Bridgeman et al. reported that the addition of trametinib could overcome acquired sunitinib resistance in renal cell carcinoma xenograft models37, which supports our conclusion that inhibition of ERK1/2 phosphorylation may be a key to overcome the acquired resistance to antiangiogenic tyrosine kinase inhibitors. This evidence concerns the gene MAPK3 and hereditary clear cell renal cell carcinoma.