Page 164 - ebook HCC

162 PROGRAMME AND ABSTRACTS GENEVA, SWITZERLAND EASL HCC SUMMIT 163
FEBRUARY 13 - 16, 2014

MOLECULAR PATHOGENESIS AND INTEGRATION WITH A MOLECULAR
TRANSLATIONAL RESEARCH CLASSIFICATION OF CIRRHOSIS

Josep M Llovet 1 2 Yujin Hoshida 1
1 ICREA , BCLC , Liver Unit, IDIBAPS, Hospital Clínic Barcelona, Barcelona, Spain, 1 Icahn Scool of Medicine at Mount Sinai, New York, United States
2 Mount Sinai Liver Cancer Program, Icahn School of Medicine at Mount Sinai,
New York, United States Corresponding author’s e-mail: yujin.hoshida@mssm.edu

Corresponding author’s e-mail: jmllovet@clinic.ub.es
Prognostic prediction is a key issue for better clinical management of liver cirrhosis and
hepatocellular carcinoma (HCC). Studies have revealed that genomic profile of diseased
Liver cancer is the second cause of cancer mortality and a major health problem globally. liver is a source of molecular information predictive of variety of clinical outcomes such
Only one molecular therapy, sorafenib, has been approved for advanced cases. There is as intrahepatic tumor metastasis, multi-centric HCC development, cirrhosis progression,
limited understanding of the pathogenesis of the disease. The field-effect predisposing and death. It is also known that the prognostic information harbored in diseased liver is
to HCC development is characterized by activation of signaling pathways related to IL- independent of HCC tumor and complementary to each other. Integration of these different
signaling, oxidative stress, EGF signaling and inflammation among other. Mutations in types of prognostic information will improve precision of prognostic prediction and enable
promoter regions of TERT have been identified in 25% of cases in preneoplastic lesions. more personalized patient management. For example, molecular biomarkers of HCC
Also inactivation of p53 in stellate cells appears to be a potential gatekeeper. During the risk will guide HCC surveillance as well as follow-up after curative surgery or ablation
last decade and after applying next generation sequencing several drivers have been of primary HCC tumors. In addition, such information may provide clues to treat and/
identified. Each HCC contains around 35-40 mutations, among which 6-8 are considered or prevent molecular drivers of poor prognosis and facilitate development of companion
drivers. The main mutations described are in the promoter region of TERT, p53, CTNNB1, biomarkers.
ARIDA1A and Axin 1. Afterwards the landscape of mutations is characterized by a long
CLINICAL SPEAKERS ABSTRACTS and FGF19 and 6p21 VEGFA, whereas other amplifications described contain Myc and CLINICAL SPEAKERS ABSTRACTS
tail of mutated genes in <5% of cases, such as RAS, PI3K and others. In terms of high
level amplifications at 5-10% prevalence containing oncogenes are in 11q13 Cyclin D1
Met among others. All this molecular information should be directed to select populations
for proof-of concept trials, such as the one testing MEK inhibitors in RAS+ patients, or trial
enrichment, such as the one testing MET inhibitors in MET –positive populations.