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Mammalian target of rapamycin (mTOR) pathway signalling in lymphomas

Published online by Cambridge University Press:  04 February 2008

Elias Drakos ,
George Z. Rassidakis  and
L. Jeffrey Medeiros
Elias Drakos
Affiliation:
Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
George Z. Rassidakis
Affiliation:
Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. First Department of Pathology, National and Kapodistrian University of Athens, Athens, Greece.
L. Jeffrey Medeiros*
Affiliation:
Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
*
*Corresponding author: L. Jeffrey Medeiros, Department of Hematopathology, Unit 72, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA. Tel: +1 713 794 5446; Fax: +1 713 745 0736; Email: ljmedeiros@mdanderson.org
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Abstract

The mammalian target of rapamycin mTOR is a central element in an evolutionary conserved signalling pathway that regulates cell growth, survival and proliferation, orchestrating signals originating from growth factors, nutrients or particular stress stimuli. Two important modulators of mTOR activity are the AKT and ERK/MAPK signalling pathways. Many studies have shown that mTOR plays an important role in the biology of malignant cells, including deregulation of the cell cycle, inactivation of apoptotic machinery and resistance to chemotherapeutic agents. The development of several mTOR inhibitors, in addition to rapamycin, has facilitated studies of the role of mTOR in cancer, and verified the antitumour effect of mTOR inhibition in many types of neoplasms, including lymphomas. Clinical trials of rapamycin derivatives in lymphoma patients are already in development and there are encouraging preliminary results, such as the substantial response of a subset of mantle cell lymphoma patients to the rapamycin analogue temsirolimus. Based on results obtained from in vitro and in vivo studies of the mTOR pathway in lymphomas, it seems that better understanding of mTOR regulation will reveal aspects of lymphomagenesis and contribute to the development of more powerful, targeted therapies for lymphoma patients.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 10 , October 2008 , e4
Copyright
Copyright © Cambridge University Press 2008

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References

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Further reading, resources and contacts

Guertin, D.A. and Sabatini, D.M. (2007) Defining the role of mTOR in cancer. Cancer Cell 12, 9-22CrossRefGoogle ScholarPubMed
Jaffe, E. et al. (eds) (2001) Pathology and Genetics of Tumors of Hematopoietic and Lymphoid Tissues. World Health Organization Classification of Tumours, IARC Press, LyonGoogle Scholar
http://www.cancer.gov/clinicaltrials and http://www.citeline.com.Google Scholar