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Targeting the Mammalian Target of Rapamycin (mTOR) in Cancer Therapy: Lessons from Past and Future Perspectives
Department of Visceral Surgery, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Pavillon 3, Av. de Beaumont, Lausanne 1011, Switzerland
* Author to whom correspondence should be addressed.
Received: 6 April 2011; in revised form: 13 May 2011 / Accepted: 16 May 2011 / Published: 24 May 2011
Abstract: Over the last decade, extensive studies have been made to understand the role played by the mammalian target of rapamycin (mTOR) in cancer. Knowledge in this field has been gained from discoveries in basic research as well as from observations made in patients treated with allosteric mTOR inhibitors such as rapamycin. Despite promising preclinical studies, targeting mTOR in cancer therapy has shown limited clinical benefits so far. However, recent findings have revealed the complexity of the functions of mTOR in cancer and have helped develop new strategies to improve the anticancer efficacy of mTOR inhibitors. In particular, a complex network between mTOR and other signaling pathways has been identified that influences the anticancer efficacy of mTOR inhibitors. In addition, an emerging role of mTOR in the tumor microenvironment has been suggested. In this review, we confront the major findings that have been made in the past, both in experimental settings as well as in clinical trials. We further review the strategies that have been designed to further improve the efficacy of therapies targeting mTOR.
Keywords: cancer; mTOR; rapalogs; signaling; therapy
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Dufour, M.; Dormond-Meuwly, A.; Demartines, N.; Dormond, O. Targeting the Mammalian Target of Rapamycin (mTOR) in Cancer Therapy: Lessons from Past and Future Perspectives. Cancers 2011, 3, 2478-2500.
Dufour M, Dormond-Meuwly A, Demartines N, Dormond O. Targeting the Mammalian Target of Rapamycin (mTOR) in Cancer Therapy: Lessons from Past and Future Perspectives. Cancers. 2011; 3(2):2478-2500.
Dufour, Marc; Dormond-Meuwly, Anne; Demartines, Nicolas; Dormond, Olivier. 2011. "Targeting the Mammalian Target of Rapamycin (mTOR) in Cancer Therapy: Lessons from Past and Future Perspectives." Cancers 3, no. 2: 2478-2500.