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Mechanisms of Disease: survival benefit of temsirolimus validates a role for mTOR in the management of advanced RCC

Nature Clinical Practice Oncology volume 5, pages 601–609 (2008)Cite this article

Abstract

Temsirolimus is a specific inhibitor of mammalian target of rapamycin (mTOR) that is approved for the treatment of advanced renal cell carcinoma. mTOR is unique among antitumor drug targets because it is a convergence point for many signaling pathways. Activation of mTOR by various growth signals increases the synthesis of proteins needed for cell-cycle progression and tumor growth. Temsirolimus demonstrates a significant improvement in overall survival in patients with advanced renal cell carcinoma and poor-prognostic features, thereby validating the importance of mTOR in the natural history of this disease. mTOR might also be an important target in other tumor types, and more than 100 ongoing clinical trials are designed to identify additional malignancies that respond to temsirolimus and other mTOR inhibitors, either alone or in combination with other targeted agents or chemotherapy.

Key Points

  • In normal cells, mTOR is a central controller for the synthesis of proteins that regulate cell proliferation and growth

  • In some tumor types, mTOR has a key role in the cell cycle and synthesis of angiogenic proteins

  • Single-agent temsirolimus has demonstrated significant improvement in overall survival versus interferon-α in patients with advanced renal cell carcinoma and poor prognostic features, and has thereby validated the clinical importance of mTOR activity in the biology of this disease

  • Various strategies are being explored to identify tumor types for which mTOR is an important therapeutic target

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Figure 1: Signal transduction pathways involving mTOR.

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Acknowledgements

Wyeth Pharmaceuticals provided support for the preparation of this manuscript. The author thanks Peloton Advantage for assistance with manuscript preparation.

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  1. Division of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Care Center, 1500 East Duarte Road, Duarte, CA 91010, USA rfiglin@coh.org

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  1. Division of Medical Oncology and Therapeutics Research, RA Figlin is Arthur and Rosalie Kaplan Professor of Oncology and Chair, City of Hope National Medical Center and Beckman Research Institute, and Associate Director of Clinical Research, City of Hope Comprehensive Cancer Center, Duarte, California, USA.,

    Robert A Figlin

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Robert A Figlin is a consultant for and receives grant/research support from Wyeth Pharmaceuticals.

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Figlin, R. Mechanisms of Disease: survival benefit of temsirolimus validates a role for mTOR in the management of advanced RCC. Nat Rev Clin Oncol 5, 601–609 (2008). https://doi.org/10.1038/ncponc1173

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