TKIs in renal cell carcinoma: What can we expect in the future?

Kidney cancer represents 5% of all new cancer diagnoses and is commonly associated with the loss of function of the von Hippel–Lindau (VHL) tumor-suppressor protein and as a consequence aberrant signaling by tyrosine kinases. This observation has led to the use of tyrosine-kinase inhibitors (TKIs) as targeted therapies revolutionizing the treatment of metastatic kidney cancer and improving patient survival as both first-line and second-line therapies. Multiple clinical trials have established improved treatment strategies to maximize patient response. Despite these advances issues still remain regarding side-effects of TKI-treatment and biomarkers are required to predict which patients will derive maximum benefit from TKI-therapy, as well as to monitor drug response. Resistance to TKI-therapy occurs upon prolonged treatment and recent studies have investigated the combination of TKIs with newer immunotherapies to improve patient response. This review discusses clinically approved TKIs, current TKI-based clinical trials and potential future drug-combinations for use in treatment.