Despite improvements in overall survival being achieved with the use of targeted therapies, the onset of resistance to treatment is virtually inevitable. In a translational study, researchers demonstrated enhanced stability of the antiapoptotic protein MCL-1, which resulted in an increase in mTORC1 activity in cancer cells exposed to clinically relevant doses of the tyrosine-kinase inhibitor sunitinib. Exposure to doses of sunitinib higher than those used clinically resulted in a decline in MCL-1 levels and inhibition of mTOR signalling. Further investigations revealed that the effects of sunitinib are mediated by proteasomal degradation of MCL-1. Analysis of MCL-1 and mTORC1 expression in tumour samples from patients with renal cell carcinoma, or neuroendocrine tumours revealed a significant association between MCL-1 expression and resistance to sunitinib.