New strategies in kidney cancer: therapeutic advances through understanding the molecular basis of response and resistance.

The emergence of viable therapeutic strategies in metastatic renal cell carcinoma has invigorated translational and clinical research in this disease. Building upon the clinical activity observed with inhibition of vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways, novel strategies are being investigated to extend existing clinical benefits. Preclinical study has identified potential molecular mechanisms of response and resistance, providing a rational basis for biomarker development as well as sequential and combination therapy strategies. Several treatment strategies have emerged that are in the early phases of clinical testing. Further clinical and translational research is needed to validate initial hypotheses and translate observations into novel treatment strategies.