Mechanisms of acquired resistance to sunitinib in an RCC patient

Sunitinib is one of the most widely used targeted therapeutics for renal cell-cancer (RCC), but acquired resistance against targeted therapies remains a major clinical challenge. To dissect mechanisms of acquired resistance and unravel reliable predictive biomarkers for sunitinib in renal cell-cancer (RCC), we sequenced the exons of 409 tumor-suppressor genes and oncogenes in paired tumor samples from an RCC patient, obtained at baseline and following acquired resistance to sunitinib. From newly arising mutations, we selected, using in-silico prediction models, 6 predicted to be deleterious and mechanistically validated their relevance in the model