Currently, numerous mechanisms underlying reduced sensitivity to sunitinib in RCC, including lysosomal sequestration of TKIs, gene mutations and modifications of gene expression levels, the angiogenic switch, constitutive activation of AKT/mTOR signaling, ATP-binding cassette (ABC) efflux transporters, tumor heterogeneity and the tumor microenvironment, have been investigated [38–40]. This evidence concerns the gene ABCB6 and renal cell carcinoma.