Liver Transplant Research Today is a free monthly online journal that collates and summarizes the latest research about Liver Transplant, including details on risks, prognosis, procedure, surgery, organ donation.

Mammalian target of rapamycin pathway activity in hepatocellular carcinomas of patients undergoing liver transplantation.

Sieghart W, Fuereder T, Schmid K, Cejka D, Werzowa J, Wrba F, Wang X, Gruber D, Rasoul-Rockenschaub S, Peck-Radosavljevic M, Wacheck V

Department of Clinical Pharmacology, Section of Experimental Oncology/Molecular Pharmacology, Medical University Vienna, Vienna, Austria.

BACKGROUND: Because mammalian target of rapamycin (mTOR) inhibitors combine anticancer and immunosuppressive properties we investigated: 1) the activation status and prognostic significance of the mTOR pathway in hepatocellular carcinoma (HCC) tissues of patients undergoing orthotopic liver transplantation (OLT) for HCC, and 2) the single and combinatorial efficacy of RAD001 in HCC cells. METHODS: PTEN, p-AKT, p-mTOR, p-p70S6K, and p-4EBP-1 were analyzed by immunohistochemistry in explanted HCCs of 166 patients undergoing OLT. Efficacy of RAD001 as mono- and combination therapy with doxorubicin was tested in Hep3B and SNU398 cells. RESULTS: The mTOR pathway is activated in about 40% of patients undergoing OLT for HCC but no direct correlation between up- and downstream proteins was observed. We found no influence of mTOR pathway protein expression on disease free survival (DFS) or overall survival (OS). There was a marked single agent and chemo-sensitizing effect of RAD001 against HCC cells in vitro. CONCLUSION: The mTOR pathway is active in 40% of patients with HCC undergoing OLT, but has no influence of DFS or OS. No direct correlation was observed between up- and downstream proteins limiting the use of upstream proteins to predict mTOR activity. Prospective clinical trials are needed to test whether the activation status of the mTOR pathway in HCCs predicts the antitumor effect of rapamycin derivative in the posttransplantation course.

Published 23 February 2007 in Transplantation, 83(4): 425-32.
Full-text of this article is available online (may require subscription).

© 2005-2008 Liver Transplant Research Today. All Rights Reserved.