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©2014 Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Nov 27, 2014; 6(11): 776-782
Published online Nov 27, 2014. doi: 10.4254/wjh.v6.i11.776
Published online Nov 27, 2014. doi: 10.4254/wjh.v6.i11.776
Mammalian target of rapamycin inhibition in hepatocellular carcinoma
René E Ashworth, Hematology and Medical Oncology Program, NYU School of Medicine, Perlmutter Cancer Center, NYU Langone Medical Center, Division of Hematology and Oncology, New York, NY 10016, United States
Jennifer Wu, NYU School of Medicine, Subdivision of GI Oncology, Perlmutter Cancer Center, NYU Langone Medical Center, Division of Hematology and Oncology, New York, NY 10016, United States
Author contributions: Ashworth RE conducted literature review, drafted manuscript and provided all figures; Wu J provided the theme and layout for the review, edited manuscript, and provided final approval.
Correspondence to: Jennifer Wu, MD, Assistant Professor of Medicine, NYU School of Medicine, Subdivision of GI Oncology, Perlmutter Cancer Center, NYU Langone Medical Center, Division of Hematology and Oncology, 550 First Avenue, BCD 556, New York, NY 10016, United States. jennifer.wu@nyumc.org
Telephone: +1-212-2636485 Fax: +1-212-2638210
Received: July 29, 2014
Revised: September 13, 2014
Accepted: October 1, 2014
Published online: November 27, 2014
Processing time: 114 Days and 13 Hours
Revised: September 13, 2014
Accepted: October 1, 2014
Published online: November 27, 2014
Processing time: 114 Days and 13 Hours
Core Tip
Core tip: Advanced hepatocellular carcinoma (HCC) has a poor prognosis with limited therapeutic options. The mammalian target of rapamycin (mTOR) pathway (regulated by mTORC1 and mTORC2) is implicated in HCC pathogenesis. This review examines pre-clinical and clinical data demonstrating that mTORC1 inhibition effectively prevents HCC recurrence post-liver transplantation, and also has a modest anti-tumor effect in advanced HCC. The rationale and preclinical data for utilizing dual mTOR (mTORC1 and mTORC2) inhibition in HCC is also reviewed; a current phase I clinical trial to investigate the efficacy of dual mTOR inhibitors is briefly discussed. mTOR pathway inhibition has therapeutic potential in the treatment of advanced HCC.