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Targeting mTOR Signaling Pathways in Liver Disease

  • Hala E. Thomas
  • Sara C. KozmaEmail author
Chapter

Abstract

Over the last 15 years, the Ser/Thr protein kinase mammalian target of rapamycin (mTOR) has emerged as a critical regulator of cell growth, proliferation, apoptosis, and metabolism [1]. The diversity of intracellular responses, in which mTOR is implicated, stems from the fact that it integrates input from distinct signaling effectors (growth factors and nutrients) and acts on specific substrates depending on its ­interaction in multienzyme protein complexes termed mTOR complexes [1]. In addition, mTOR signaling is negatively regulated by several tumor suppressors. In a largely selective manner, the macrolide antibiotic rapamycin inhibits the activity of one of the mTOR complexes, mTOR Complex1 (mTORC1, see below). Rapamycin (sirolimus) and its derivatives (AP23573, CCI-779, and RAD001) are used in the clinic as immunosuppressive agents in organ transplantation and as antiproliferative and antiangiogenic agents to prevent coronary restenosis and treat cancer. Here, we will review the molecular mechanisms known to regulate mTOR signaling pathways, illustrate the role of mTOR signaling in liver disease, and report on the preclinical and clinical studies targeting mTOR to treat liver cancer.

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© Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  1. 1.Genome Research InstituteUniversity of CincinnatiCincinnatiUSA

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