Drug repurposing identifies a synergistic high-order drug combination to treat sunitinib-resistant renal cell carcinoma

We report that in response to combination treatment with a synergistic low-dose four-drug combination, human Caki-1 cells resistant to sunitinib alter their pheno- and genotype. We detected that the metabolism of these cells is altered. Gene expression analysis revealed significant differential expression of genes related to mitosis, apoptosis and cell attachment. We detected regulation changes in enzymes mediating the ceramide and sphingolipid metabolism. Overall design: The experiments have been designed to analyze the effect of a multidrug combination consisting of Rapta-C, erlotinib, metformin and parthenolide in the human Caki-1 cell line resistant to treatment with the small molecule-based targeted drug sunitinib.