Targeting Receptor Tyrosine Kinase Pathways in Hepatocellular Carcinoma

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)

Volume 17, 14 Issues, 2017

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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Michelle Prudhomme
Institut de Chimie de Clermont-Ferrand
Université Clermont Auvergne

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Targeting Receptor Tyrosine Kinase Pathways in Hepatocellular Carcinoma

Anti-Cancer Agents in Medicinal Chemistry, 11(6): 560-575.

Author(s): Hung Huynh, Richard Wei Jie Ong, Peter Yi Qing Li, Swee Shean Lee, Shu Yang, Lih Wen Chong, Danh Anh Tuan Luu, Chun Tzen Jong and Irene Wei Ling Lam.

Affiliation: Laboratory of Molecular Endocrinology, Division of Molecular and Cellular Research, National Cancer Centre, 11 Hospital Drive, Singapore 169610.


Hepatocellular cancer (HCC) is the fifth most common malignancy worldwide with 660,000 deaths annually. Studies of the molecular pathophysiology of HCC have shown that growth factors and their corresponding receptors are commonly overexpressed and/or dysregulated in HCC. Activation of these receptors and their downstream signaling pathways can lead to angiogenesis, cell proliferation, survival and metastasis of HCC. Hence, agents that specifically block their activation and signaling cascades would be valuable for treatment of HCC. Many small molecular tyrosine kinase inhibitors (TKIs) and antibodies have been tested in various phases of clinical trials. Although sorafenib has been shown to improve overall survival of patients with advanced HCC, the improvement is marginal and many patients eventually turn out to be refractory to this therapy. Thus, there is a pressing need to identify new drugs and effective treatments for this fatal disease. This review summarizes the pre-clinical and clinical data on the efficacy of the emerging tyrosine kinase inhibitors as well as the rationale for combination therapies for advanced HCC treatment. Understanding the mechanisms of action of these therapeutic agents and methods of combining these drugs may help to increase their efficacy, reduce toxicity, and improve overall survival and quality of life in patients with HCC.


Hepatocellular carcinoma, targeted therapies, tyrosine kinase inhibitors, growth factor receptor, TKIs, DCE-MRI, VEGF, DCE-MRI parameters, VEGFR-2, VEGF inhibition, Dovitinib lactate, PI3K/Akt/mTOR PATHWAY, IMC-A12, therapeutic modality, Jak/Stat pathway.

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Article Details

Volume: 11
Issue Number: 6
First Page: 560
Last Page: 575
Page Count: 16
DOI: 10.2174/187152011796011055
Price: $58

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