Mechanisms of sunitinib resistance in renal cell carcinoma and associated opportunities for therapeutics

Sunitinib is the first-line drug for renal cell carcinoma (RCC) treatment. However, patients who received sunitinib treatment will ultimately develop drug resistance after 6-15 months, creating a huge obstacle to the current treatment of renal cell carcinoma. Therefore, it is urgent to clarify the mechanisms of sunitinib resistance and develop new strategies to overcome it. In this review, the mechanisms of sunitinib resistance in renal cell carcinoma have been summarized based on five topics: activation of bypass or alternative pathway, inadequate drug accumulation, tumour microenvironment, metabolic reprogramming and epigenetic regulation. Furthermore, present and potential biomarkers, as well as potential treatment strategies for overcoming sunitinib resistance in renal cell carcinoma, are also covered.