Gastroenterology
Volume 135, Issue 6 , Pages 1972-1983.e11, December 2008

Pivotal Role of mTOR Signaling in Hepatocellular Carcinoma

  • Augusto Villanueva

      Affiliations

    • Mount Sinai Liver Cancer Program, Divisions of Liver Diseases and Hemato/Oncology, Department of Medicine, Human Genetics, Department of Genetics and Genomic Sciences, Surgical Oncology, Department of Surgery, Department of Pathology, Mount Sinai School of Medicine, New York, New York
    • ,
  • Derek Y. Chiang

      Affiliations

    • Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts
    • Cancer Program, The Broad Institute of Harvard and MIT, Cambridge, Massachusetts
    • Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
    • ,
  • Pippa Newell

      Affiliations

    • Mount Sinai Liver Cancer Program, Divisions of Liver Diseases and Hemato/Oncology, Department of Medicine, Human Genetics, Department of Genetics and Genomic Sciences, Surgical Oncology, Department of Surgery, Department of Pathology, Mount Sinai School of Medicine, New York, New York
    • ,
  • Judit Peix

      Affiliations

    • Mount Sinai Liver Cancer Program, Divisions of Liver Diseases and Hemato/Oncology, Department of Medicine, Human Genetics, Department of Genetics and Genomic Sciences, Surgical Oncology, Department of Surgery, Department of Pathology, Mount Sinai School of Medicine, New York, New York
    • ,
  • Swan Thung

      Affiliations

    • Mount Sinai Liver Cancer Program, Divisions of Liver Diseases and Hemato/Oncology, Department of Medicine, Human Genetics, Department of Genetics and Genomic Sciences, Surgical Oncology, Department of Surgery, Department of Pathology, Mount Sinai School of Medicine, New York, New York
    • ,
  • Clara Alsinet

      Affiliations

    • BCLC Group, Liver Unit, HCC Translational Research Laboratory and Department of Pathology, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas, Hospital Clínic, Barcelona, Spain
    • ,
  • Victoria Tovar

      Affiliations

    • BCLC Group, Liver Unit, HCC Translational Research Laboratory and Department of Pathology, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas, Hospital Clínic, Barcelona, Spain
    • ,
  • Sasan Roayaie

      Affiliations

    • Mount Sinai Liver Cancer Program, Divisions of Liver Diseases and Hemato/Oncology, Department of Medicine, Human Genetics, Department of Genetics and Genomic Sciences, Surgical Oncology, Department of Surgery, Department of Pathology, Mount Sinai School of Medicine, New York, New York
    • ,
  • Beatriz Minguez

      Affiliations

    • Mount Sinai Liver Cancer Program, Divisions of Liver Diseases and Hemato/Oncology, Department of Medicine, Human Genetics, Department of Genetics and Genomic Sciences, Surgical Oncology, Department of Surgery, Department of Pathology, Mount Sinai School of Medicine, New York, New York
    • ,
  • Manel Sole

      Affiliations

    • BCLC Group, Liver Unit, HCC Translational Research Laboratory and Department of Pathology, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas, Hospital Clínic, Barcelona, Spain
    • ,
  • Carlo Battiston

      Affiliations

    • Gastrointestinal Surgery and Liver Transplantation Unit, National Cancer Institute, Milan, Italy
    • ,
  • Stijn van Laarhoven

      Affiliations

    • Mount Sinai Liver Cancer Program, Divisions of Liver Diseases and Hemato/Oncology, Department of Medicine, Human Genetics, Department of Genetics and Genomic Sciences, Surgical Oncology, Department of Surgery, Department of Pathology, Mount Sinai School of Medicine, New York, New York
    • ,
  • Maria I. Fiel

      Affiliations

    • Mount Sinai Liver Cancer Program, Divisions of Liver Diseases and Hemato/Oncology, Department of Medicine, Human Genetics, Department of Genetics and Genomic Sciences, Surgical Oncology, Department of Surgery, Department of Pathology, Mount Sinai School of Medicine, New York, New York
    • ,
  • Analisa Di Feo

      Affiliations

    • Mount Sinai Liver Cancer Program, Divisions of Liver Diseases and Hemato/Oncology, Department of Medicine, Human Genetics, Department of Genetics and Genomic Sciences, Surgical Oncology, Department of Surgery, Department of Pathology, Mount Sinai School of Medicine, New York, New York
    • ,
  • Yujin Hoshida

      Affiliations

    • Cancer Program, The Broad Institute of Harvard and MIT, Cambridge, Massachusetts
    • Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
    • ,
  • Steven Yea

      Affiliations

    • Mount Sinai Liver Cancer Program, Divisions of Liver Diseases and Hemato/Oncology, Department of Medicine, Human Genetics, Department of Genetics and Genomic Sciences, Surgical Oncology, Department of Surgery, Department of Pathology, Mount Sinai School of Medicine, New York, New York
    • ,
  • Sara Toffanin

      Affiliations

    • Mount Sinai Liver Cancer Program, Divisions of Liver Diseases and Hemato/Oncology, Department of Medicine, Human Genetics, Department of Genetics and Genomic Sciences, Surgical Oncology, Department of Surgery, Department of Pathology, Mount Sinai School of Medicine, New York, New York
    • ,
  • Alex Ramos

      Affiliations

    • Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts
    • Cancer Program, The Broad Institute of Harvard and MIT, Cambridge, Massachusetts
    • Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
    • ,
  • John A. Martignetti

      Affiliations

    • Mount Sinai Liver Cancer Program, Divisions of Liver Diseases and Hemato/Oncology, Department of Medicine, Human Genetics, Department of Genetics and Genomic Sciences, Surgical Oncology, Department of Surgery, Department of Pathology, Mount Sinai School of Medicine, New York, New York
    • ,
  • Vincenzo Mazzaferro

      Affiliations

    • Gastrointestinal Surgery and Liver Transplantation Unit, National Cancer Institute, Milan, Italy
    • ,
  • Jordi Bruix

      Affiliations

    • BCLC Group, Liver Unit, HCC Translational Research Laboratory and Department of Pathology, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas, Hospital Clínic, Barcelona, Spain
    • ,
  • Samuel Waxman

      Affiliations

    • Mount Sinai Liver Cancer Program, Divisions of Liver Diseases and Hemato/Oncology, Department of Medicine, Human Genetics, Department of Genetics and Genomic Sciences, Surgical Oncology, Department of Surgery, Department of Pathology, Mount Sinai School of Medicine, New York, New York
    • ,
  • Myron Schwartz

      Affiliations

    • Mount Sinai Liver Cancer Program, Divisions of Liver Diseases and Hemato/Oncology, Department of Medicine, Human Genetics, Department of Genetics and Genomic Sciences, Surgical Oncology, Department of Surgery, Department of Pathology, Mount Sinai School of Medicine, New York, New York
    • ,
  • Matthew Meyerson

      Affiliations

    • Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts
    • BCLC Group, Liver Unit, HCC Translational Research Laboratory and Department of Pathology, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas, Hospital Clínic, Barcelona, Spain
    • ,
  • Scott L. Friedman

      Affiliations

    • Mount Sinai Liver Cancer Program, Divisions of Liver Diseases and Hemato/Oncology, Department of Medicine, Human Genetics, Department of Genetics and Genomic Sciences, Surgical Oncology, Department of Surgery, Department of Pathology, Mount Sinai School of Medicine, New York, New York
    • ,
  • Josep M. Llovet

      Affiliations

    • Mount Sinai Liver Cancer Program, Divisions of Liver Diseases and Hemato/Oncology, Department of Medicine, Human Genetics, Department of Genetics and Genomic Sciences, Surgical Oncology, Department of Surgery, Department of Pathology, Mount Sinai School of Medicine, New York, New York
    • BCLC Group, Liver Unit, HCC Translational Research Laboratory and Department of Pathology, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas, Hospital Clínic, Barcelona, Spain
    • Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain
    • Corresponding Author InformationAddress requests for reprints to: Josep M. Llovet, MD, Division of Liver Diseases, Box 1123, Mount Sinai School of Medicine, 1425 Madison Avenue, 11F-70, New York, New York 10029

Received 30 January 2008; accepted 14 August 2008. published online 22 August 2008.

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 The authors would like to honor the memory of their colleague and friend, Eric R. Lemmer, member of the Mount Sinai Liver Cancer Program and the Division of Liver Diseases. The authors also want to thank Dr Ron Prywes (Columbia University, NY) for providing the c-fos luciferase reporter. The authors thank Novartis Pharma for providing the drugs (AEE788 and RAD001 in the context of an MTA) used in this study.

 The authors disclose the following: Supported by a grant from Fundación Pedro Barrié de la Maza, Asociación Española para el Estudio del Hígado, National Cancer Center, and an European Association for the Study of the Liver-Sheila Sherlock Fellowship (A.V.); by a grant from Instituto de Salud Carlos III (FIS-CM04/00044 to B.M.); by the Italian Association for Cancer Research and the Italian National Ministry of Health (V.M.); by a grant from Instituto Carlos III (ISCIII/FIS PI 05-0150 to J.B.); by Institució Catalana de Recerca i Estudis Avançats and grants from the U.S. National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK076986-01), the Samuel Waxman Cancer Research Foundation, and the Spanish National Health Institute (SAF-2007-61898) (J.L.); and by grants from the National Institutes of Health (1RO1DK37340-23 to S.F.). Philippa Newell is a recipient of an American Liver Foundation Fellowship and Yujin Hoshida is a recipient of a Charlie A. King Trust fellowship. M. Meyerson is a consultant for Novartis.

PII: S0016-5085(08)01517-5

doi:10.1053/j.gastro.2008.08.008

Gastroenterology
Volume 135, Issue 6 , Pages 1972-1983.e11, December 2008

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