Molecular and functional analysis of sunitinib resistance induction in human renal cell carcinoma cells

We report that in response to chronic treatment with the small molecule-based targeted drug sunitinib, human Caki-1 cells alter their pheno- and genotype. We detected that the metabolism of sunitinib is still functional, but sunitinib and its N-desethyl metabolite are accumulated in the interios (lysosmes). Gene expression analysis revealed significant differential expression of genes related to mitosis, apoptosis and cell attachment. We detected potential upregulation of autophagy. The experiments have been designed to analyze the genetic changes induced in the human Caki-1 cell line acquiring resistance in response to chronic treatment with the small molecule-based targeted drug sunitinib.