RAD-001: future directions

The clinical activity of inhibitors of the mammalian target of rapamycin (mTOR) has clearly been demonstrated in patients with renal cell carcinoma. mTOR and its kinase activity is regulated by a series of upstream and downstream elements that include phosphoinositide 3-kinase (PI3K), Akt, and the tumor suppressor phosphatase and tensin homolog (PTEN). A series of preclinical and clinical findings have provided proof of principle demonstrating the relevance of this pathway in renal cell carcinoma (RCC) pathogenesis and progression. The activity of the mTOR inhibitors temsirolimus and everolimus in advanced RCC is reviewed briefly, and the future directions with this class of agents in the therapy of advanced renal cell carcinoma discussed.