Targeted Oncology

, Volume 6, Issue 1, pp 5-16

First online:

Future directions of mammalian target of rapamycin (mTOR) inhibitor therapy in renal cell carcinoma

  • Sumanta Kumar PalAffiliated withDivision of Genitourinary Malignancies, Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center Email author 
  • , Robert A. FiglinAffiliated withDivision of Hematology Oncology, Department of Medicine, Cedars-Sinai Medical CenterAcademic Program Development, Samuel Oschin Comprehensive Cancer InstituteDavid Geffen School of Medicine at UCLA

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With an explosion of available treatments for metastatic renal cell carcinoma (mRCC) in recent years, it is important to recognize that approved targeted therapies fall broadly into only two mechanistic categories. The first category, vascular endothelial growth factor (VEGF)-directed therapies, includes sunitinib, pazopanib, sorafenib and bevacizumab. The second category includes inhibitors of the mammalian target of rapamycin (mTOR), namely everolimus and temsirolimus. A pivotal trial of everolimus supports use of the agent in patients with mRCC refractory to VEGF- tyrosine kinase inhibitors (TKI) therapy, while pivotal data for temsirolimus supports use in poor-prognosis patients as first-line therapy. Multiple reviews exist to delineate the laboratory and clinical development of mTOR inhibitors. This paper will outline the future applications of these therapies. It will explore ongoing trials evaluating combinations of mTOR inhibitors with other targeted therapies, along with sequencing strategies and biomarker discovery efforts. The application of mTOR inhibitors in unique populations is also described.


mTOR Everolimus Temsirolimus Deferolimus INTORACT TORAVA BeST Biomarkers Clinical trials