Expert Reviews in Molecular Medicine: http://www.expertreviews.org/
DOI: 10.1017/S1462399408000586; 4 February 2008
Elias Drakos, George Z. Rassidakis and L. Jeffrey Medeiros (2008) Mammalian target of rapamycin (mTOR) pathway signalling in lymphomas. Expert Rev. Mol. Med. Vol. 10, e4, DOI: 10.1017/S1462399408000586

Mammalian target of rapamycin (mTOR) pathway signalling in lymphomas

Elias Drakos ^a1, George Z. Rassidakis ^a2 and L. Jeffrey Medeiros ^{a1 c1}

^a1 Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.

^a2 First Department of Pathology, National and Kapodistrian University of Athens, Athens, Greece

^c1 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

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.

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