Abstract
Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide. Unresectable or metastatic HCC has a poor prognosis, and systemic cytotoxic chemotherapy has failed to show a substantial benefit for patients with HCC. However, there has been increasing interest in developing novel molecularly targeted agents in HCC due to the accumulation of knowledge of cell signaling and molecular carcinogenesis. Furthermore, some of these agents have proven to be efficacious in other traditionally challenging carcinomas, such as renal cell carcinoma. Recently, a phase III, randomized, placebo-controlled trial demonstrated that sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor and Ras kinase, improves overall survival (OS) in patients with advanced HCC. This seminal study described the first agent to improve OS in HCC and began a new era of molecule-targeted cancer therapies. Currently, many novel molecularly targeted agents are under evaluation in clinical trials. In this review, we comprehensively summarize the molecular pathogenesis, targets, and signal transduction pathways involved in HCC. We also detail the current status of molecularly targeted agents that are under clinical development in advanced HCC, including the mechanisms of action of these agents.
Keywords: Cell signaling, clinical trials, combination therapy, preclinical studies, efficacy, hepatocellular carcinoma, molecular carcinogenesis, molecularly targeted agents, molecular targets, safety
Current Medicinal Chemistry
Title: Evolving Molecular Mechanism-Based Strategies for Control of Hepatocellular Carcinoma
Volume: 18 Issue: 28
Author(s): K. Sato and M. Mori
Affiliation:
Keywords: Cell signaling, clinical trials, combination therapy, preclinical studies, efficacy, hepatocellular carcinoma, molecular carcinogenesis, molecularly targeted agents, molecular targets, safety
Abstract: Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide. Unresectable or metastatic HCC has a poor prognosis, and systemic cytotoxic chemotherapy has failed to show a substantial benefit for patients with HCC. However, there has been increasing interest in developing novel molecularly targeted agents in HCC due to the accumulation of knowledge of cell signaling and molecular carcinogenesis. Furthermore, some of these agents have proven to be efficacious in other traditionally challenging carcinomas, such as renal cell carcinoma. Recently, a phase III, randomized, placebo-controlled trial demonstrated that sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor and Ras kinase, improves overall survival (OS) in patients with advanced HCC. This seminal study described the first agent to improve OS in HCC and began a new era of molecule-targeted cancer therapies. Currently, many novel molecularly targeted agents are under evaluation in clinical trials. In this review, we comprehensively summarize the molecular pathogenesis, targets, and signal transduction pathways involved in HCC. We also detail the current status of molecularly targeted agents that are under clinical development in advanced HCC, including the mechanisms of action of these agents.
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Cite this article as:
Sato K. and Mori M., Evolving Molecular Mechanism-Based Strategies for Control of Hepatocellular Carcinoma, Current Medicinal Chemistry 2011; 18 (28) . https://dx.doi.org/10.2174/092986711797200462
DOI https://dx.doi.org/10.2174/092986711797200462 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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