The mTOR pathway in hepatic malignancies.

The mTOR pathway in hepatic malignancies.

Hepatology. 2013 Feb 13;

Authors: Bhat M, Sonenberg N, Gores G

Abstract
The mechanistic/mammalian target of rapamycin (mTOR) pathway plays a critical role in cellular metabolism, growth and proliferation, and has been evaluated as a target for therapy in various malignancies. The mTOR pathway is a major tumor-initiating pathway in hepatocellular carcinoma, with upregulation seen in up to 50% of (HCC) tumors. Metformin, which represses mTOR signaling by activating AMPK, has been shown to decrease liver carcinogenesis in population studies. mTOR inhibitors such as everolimus have been evaluated as adjunctive chemotherapy with some success, although efficacy has been limited by the lack of complete mTOR pathway inhibition. The active site mTOR inhibitors hold greater promise, given that they offer complete mTOR suppression. There is also evidence of mTOR pathway activation in cholangiocarcinoma, although its biological significance in initiating and promoting tumor progression remains ambiguous. This review article provides an overview of the complex biochemistry behind the mTOR pathway and its role in carcinogenesis, especially as it pertains to hepatic malignancies. (HEPATOLOGY 2013.).

PMID: 23408390 [PubMed - as supplied by publisher]

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