The role of mTOR in the management of solid tumors: An overview

Mammalian target of rapamycin (mTOR) is a key protein kinase controlling signal transduction from various growth factors and upstream proteins to the level of mRNA and ribosome with a regulatory effect on cell cycle progression, cellular proliferation and growth. TOR genes were discovered rather serendipitously while investigating the cause of resistance to immunosuppressant rapamycin in yeast. In normal cells, mTOR controls brilliantly the load of signals from its effectors resulting in a normal cell function. On the contrary, in various diseases and mainly in cancer this balance is lost due to mutations or overactivation of upstream pathways leading to a persistent proliferation and tumor growth. What makes mTOR attractive to researchers seems to be its key position which is on the crossroad of various signal pathways (Ras, PI3K/Akt, TSC, NF-kappa B) towards mRNA, ribosome, protein synthesis and translation of significant molecules, the uncontrolled production of which may lead to tumor proliferation and growth. Inhibition of mTOR by rapamycin (a natural product) or its analogs aims to prevent the deleterious effects of the abnormal signaling, regardless at which point of the signal pathway has the abnormality launched. Here, we will review the physiological functions of mTOR, its association to carcinogenesis and the latest evidence regarding the use of mTOR inhibitors in cancer treatment as well as future trends and aims of research. (C) 2008 Elsevier Ltd. All rights reserved.