Pathogenesis of hepatocellular carcinoma and molecular therapies
- 1 May 2009
- journal article
- review article
- Published by Ovid Technologies (Wolters Kluwer Health) in Current Opinion in Gastroenterology
- Vol. 25 (3), 186-194
- https://doi.org/10.1097/mog.0b013e32832962a1
Abstract
Over the past decades, advances in the knowledge of the molecular pathogenesis of hepatocellular carcinoma (HCC) have allowed significant improvements in the therapeutic management of this devastating disease. Several investigations have established the role of aberrant activation of major intracellular signaling pathways during human hepatocarcinogenesis. Genome-wide analysis of DNA copy number changes and gene expression led to the identification of gene signatures and novel targets for cancer treatment. Numerous attempts have tried to develop a molecular classification of HCC. This review aims to summarize the most relevant genetic alterations and pathways involved in the development and progression of HCC, providing an overview of the molecular targeted therapies tested so far in human HCC. The discovery of sorafenib, a multikinase inhibitor, as a treatment with survival benefits in patients with advanced HCC, has become a major breakthrough in the clinical management of HCC. For the first time, a molecular therapy was able to demonstrate significant efficacy for the treatment of HCC patients. New guidelines have established the ideal endpoints for the design of clinical trials for HCC. At last, a molecular classification of HCC based on genome-wide investigations, able to identify patient subclasses according to drug sensitivity will lead to a more personalized medicine. In this review, we provide a comprehensive analysis of the underlying molecular mechanisms leading to human hepatocarcinogenesis, providing the scientific rationale for the development of new therapeutic targets.Keywords
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