mTOR inhibitors in renal cell carcinoma.

The mammalian target of rapamycin (mTOR) is a downstream effector of the PI3-K/Akt/mTOR pathway. Allosteric inhibitors of mTOR, everolimus and temsirolimus, have shown promising clinical activity in advanced renal cell carcinoma but their effect is far from durable and only a subset of patients experience substantial benefit from these agents. The PI3-K/Akt/mTOR pathway represents an intricate network of fine regulation and feedback loops, and resistance to allosteric mTOR inhibitors may be embedded within this complexity. In this article we highlight the molecular elements of the PI3-K/Akt/mTOR pathway, the clinical experience with everolimus and temsirolimus in advanced renal cell carcinoma, and the future directions in terms of sequential therapy, combinational therapy and development of novel therapeutic agents.