 |
Josep M. Llovet, M.D.
Institutional Affiliation:
Director of Research Liver Cancer Program
Associate Professor of Medicine
Mount Sinai School of Medicine
http://www.mountsinai.org/Find%20A%20Faculty/profile.do?id=0000072500001497188072&officeDrawer=biz
Professor of Research
BCLC Group, Liver Unit, CIBERehd,IDIBAPS
Hospital Clínic Barcelona, Spain
Education
University of Barcelona, Spain, M.D.
Research
Molecular Classification of Hepatocellular Carcinoma and Novel Targets for Therapies
Impact
The unique strength of the clinical and translational program in Mount Sinai, along with our collaborators of Dana Farber-MIT/broad Institute, and University of Barcelona, enable to perform a high-end research in liver cancer. The main goal of the group is to explore the key drivers of oncogenesis in liver cancer, in order to provide a molecular classification of the disease. This will allow targeting these molecules with novel drugs in a more personalized mode.
Summary of Research
Hepatocellular carcinoma (HCC) represents the third-leading cause of cancer- related deaths worldwide, but only one molecular therapy –sorafenib- is effective so far. In order to accelerate the knowledge of the pathogenesis of this cancer and the development of targeted therapies, we assembled an HCC Research Program led by Dr. Josep M. Llovet and collaborators from Mount Sinai (New York), associated with an international consortium of basic and translational researchers, including Dana-Farber- MIT (Boston), Hospital Clinic (Barcelona) and National Cancer Institute (Milan). As a result of the research conducted by the group, we recently identified VEGFA high-level amplifications in HCC, demonstrated that inhibition of mTOR signaling ameliorates tumor progression in experimental models and generated a gene signature from the adjacent tumoral tissue that predicts patient outcome after surgical resection. In addition, we identified novel oncogenes, such as AEG-1, by genetic manipulation of experimental models in the context of the program Institute Without Walls.
Our immediate plans for the upcoming years are focused in assessing novel mutations in oncogenes or tumor suppressor genes (TSG) that can provide markers of early detection and identify the driving molecular events that may represent targets for molecular therapies. For that purpose, we will survey the mutation status of 141 commonly mutated genes in a large cohort of preneoplastic nodules and human HCC samples and will integrate the molecular information (i.e. mutation data, gene expression dysregulation, signaling pathway activation and progenitor cell markers) with clinical outcome to define the potential drivers in each molecular subclass. This study might identify unknown gatekeeper genes and oncogenic addiction loops in HCC patients, which will lead towards better preventive and therapeutical strategies. |
|
