The Biological Role of mTOR in the Pathogenesis of Solid Tumors: An Overview

Eleftheria      Koropouli; Leonidas      Manolopoulos; Hardev      Pandha; Konstantinos   N.   Syrigos

Abstract

The mammalian target of rapamycin (mTOR) constitutes an integrator of multiple signals and a master programmer of pivotal cellular functions such as cell growth and proliferation. Due to its complex function, it plays a substantial role in homeostasis at molecular, cellular, tissue and organism level and its aberrant activation is implicated in tumorigenesis and tumor progression. mTOR signaling depends on a number of upstream regulators such as PI3K and Akt, and a number of downstream effectors such as p70 S6 kinase 1 (S6K1) and 4E-BP1. The mTOR pathway seems to be a promising pathway in anticancer treatment and mTOR inhibitors constitute a currently emerging and evaluated class of antitumor agents. Nonetheless, the complexity and multifactorial regulation of this signal transduction pathway make it difficult to determine pivotal parameters such as the optimal therapeutic schedules and the appropriate criteria for the selection of patients most likely to respond, which will enable medical oncologists to proceed to the appropriate use of these agents in clinical setting. The complete dissection of both mTOR signaling and the adjacent pathways will enable experts to develop and implement multi-targeted treatment, which appears to be the most promising approach, due to the persistent and dynamic interaction between different signaling pathways. Under such circumstances, we will be capable of exploiting mTOR signaling and maximizing the benefit of patients. In the present review, we discuss the regulation of the mTOR signaling, pointing out its implication in the pathogenesis of solid tumors as well as its encouraging therapeutic potential.

Keywords: Mammalian target of rapamycin (mTOR), rapamycin, apoptosis, autophagy, targeted therapy

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