Role of the mTOR Pathway in Normal and Tumoral Adrenal Cells

The mammalian target of rapamycin (mTOR) is a kinase of the phosphoinositide 3-kinase (PI3Ks)/protein kinase B (PKB or AKT) signaling pathway, which is one of the most important intracellular mediators of the activity of growth factors receptors, including vascular endothelial growth factor (VEGF) and insulin-like growth factors (IGFs). Dysregulation of the mTOR pathway has been found in many human tumors. Therefore, the mTOR pathway is considered as a target for antineoplastic therapy in several malignancies. Presently, the role and functions of mTOR and its signaling pathway in the normal and pathological adrenal gland has not been clarified yet. However, many growth factors and growth factor receptors, which are considered to play a role in the pathogenesis of adrenal tumors, can at least in part exert their effects through the activation of PI3K/AKT/mTOR pathway. Dysregulation of AKT has been reported in adrenocortical carcinomas and adrenomedullary tumors, named pheochromocytomas. Adrenocortical carcinomas and malignant pheochromocytomas are aggressive tumors with poor prognosis and scant treatment options. Therefore, new treatment options are warranted for these malignancies. On the Published online: September 10, 2010 Maria Cristina De Martino Department of Internal Medicine, Division of Endocrinology, Room Ee 569 Erasmus Medical Center, Dr. Molewaterplein 50 NL–3015 GE Rotterdam (The Netherlands) Tel. +31 10 703 4394, Fax +31 10 703 5430, E-Mail demartino.mc @ gmail.com © 2010 S. Karger AG, Basel 0028–3835/10/0925–0028$26.00/0 Accessible online at: www.karger.com/nen D ow nl oa de d by : 54 .1 91 .4 0. 80 4 /2 8/ 20 17 9 :1 0: 30 P M