The impact of new data in the treatment of advanced hepatocellular carcinoma
ABSTRACT Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, causing 500,000 deaths yearly. The risk factors mostly responsible for the rising incidence of HCC in the Western hemisphere are hepatitis C, alcoholic cirrhosis, and nonalcoholic steatohepatitis, which most commonly leads to HCC in the setting of cirrhosis. Over the past 30 years, several chemotherapeutic single agents and combinations have been tested in HCC, yet none have demonstrated any improvement in survival. Recently, the multitargeted anti-angiogenic and Raf kinase inhibitor sorafenib has shown a survival advantage as a single agent and improved outcomes in combination with doxorubicin. Other novel agents have also shown intriguing outcomes as single agents (sunitinib) or in combination (bevacizumab and erlotinib). The encouraging results and clinical information gathered in recent trials are generating important clinical questions regarding which patients to treat, how to accommodate concurrent cirrhosis, and which parameters to use to monitor efficacy and the potential benefit from therapy.
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ABSTRACT: Hepatocellular carcinoma (HCC) is a major health problem, being the sixth most common cancer world-wide. Dysregulation of the balance between proliferation and cell death represents a pro-tumorigenic principle in human hepatocarcinogenesis. This review updates the recent relevant contributions reporting molecular alterations for HCC that induce an imbalance in the regulation of apoptosis. Alterations in the expression and/or activation of p53 are frequent in HCC cells, which confer on them resistance to chemotherapeutic drugs. Many HCCs are also insensitive to apoptosis induced either by death receptor ligands, such as FasL or TRAIL, or by transforming growth factor-beta (TGF-beta). Although the expression of some pro-apoptotic genes is decreased, the balance between death and survival is dysregulated in HCC mainly due to overactivation of anti-apoptotic pathways. Indeed, some molecules involved in counteracting apoptosis, such as Bcl-X(L), Mcl-1, c-IAP1, XIAP or survivin are over-expressed in HCC cells. Furthermore, some growth factors that mediate cell survival are up-regulated in HCC, as well as the molecules involved in the machinery responsible for cleavage of their pro-forms to an active peptide. The expression and/or activation of the JAK/STAT, PI3K/AKT and RAS/ERKs pathways are enhanced in many HCC cells, conferring on them resistance to apoptotic stimuli. Finally, recent evidence indicates that inflammatory processes, as well as the epithelial-mesenchymal transitions that occur in HCC cells to facilitate their dissemination, are related to cell survival. Therefore, therapeutic strategies to selectively inhibit anti-apoptotic signals in liver tumor cells have the potential to provide powerful tools to treat HCC.World Journal of Gastroenterology 03/2009; 15(5):513-20. DOI:10.3748/wjg.15.513 · 2.43 Impact Factor
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ABSTRACT: This Italian meeting, co-sponsored by the Italian Southern Oncological Group (GOIM), focused on different aspects of hepatocellular carcinoma (HCC). Topics included epidemiological studies, identification of environmental and genetic risk factors, the molecular mechanisms of pathogenesis, new diagnostic approaches and standard and novel treatment modalities. HCC remains a major health problem worldwide. It is the fifth most common cancer in the world, and the third most common cause of cancer-related death. The goal of HCC management is 'cancer control', reduction in its incidence and mortality as well as improvement in the quality of life of patients with HCC and their families. HCC epidemiology in Campania and the role of hepatitis viruses C and B in the pathogenesis of this cancer were described. Subsequently, state of the art and perspectives on the transduction pathways as therapeutic targets in HCC were evaluated. Another session was about HCC diagnosis by imaging techniques. The last session was dedicated to clinical treatment of this cancer, the role of liver transplantation, surgical resection, loco-regional procedures and systemic treatment modalities. Finally, the final results of the So.Lar. study on the Sorafenib + octreotide long-acting release (LAR) combination were presented.Expert Opinion on Investigational Drugs 04/2009; 18(3):373-8. DOI:10.1517/14712590802680158 · 5.43 Impact Factor