Abstract
Background:
Hepatocellular carcinoma (HCC) develops most often in a background of chronic inflammatory liver injury from viral infection or alcohol use. Most HCCs are diagnosed at a stage at which surgical resection is not feasible. Even in patients receiving surgery rates of recurrence and metastasis remain high. There are few effective HCC therapies and hence a need for novel, rational approaches to treatment. Platelet derived growth factor receptor-alpha (PDGFR-alpha) is involved in tumor angiogenesis and maintenance of the tumor microenvironment and has been implicated in development and metastasis of HCC.
Objective:
To examine PDGFR-alpha as a target for therapy of HCC and explore opportunities and strategies for PDGFR-alpha inhibition.
Methods:
A review of relevant literature.
Results/conclusions:
Targeted inhibition of PDGFR-alpha is a rational strategy for prevention and therapy of HCC.
MeSH terms
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Angiogenesis Inhibitors / pharmacology*
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Angiogenesis Inhibitors / therapeutic use
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Animals
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents / therapeutic use
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Benzenesulfonates / pharmacology
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Benzenesulfonates / therapeutic use
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Carcinoma, Hepatocellular / blood supply
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Carcinoma, Hepatocellular / drug therapy*
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Carcinoma, Hepatocellular / enzymology
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Carcinoma, Hepatocellular / prevention & control
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Clinical Trials as Topic
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Drug Delivery Systems
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Drug Design
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Embryonic Development / physiology
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Humans
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Liver Neoplasms / blood supply
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Liver Neoplasms / drug therapy*
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Liver Neoplasms / enzymology
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Liver Neoplasms / prevention & control
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Liver Neoplasms, Experimental / drug therapy
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Mice
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Mice, Transgenic
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Neoplasm Proteins / antagonists & inhibitors*
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Neovascularization, Pathologic / drug therapy
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Neovascularization, Physiologic / physiology
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Niacinamide / analogs & derivatives
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Phenylurea Compounds
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Protein Kinase Inhibitors / pharmacology*
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Protein Kinase Inhibitors / therapeutic use
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Protein-Tyrosine Kinases / physiology
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Pyridines / pharmacology
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Pyridines / therapeutic use
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Receptor, Platelet-Derived Growth Factor alpha / antagonists & inhibitors*
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Receptor, Platelet-Derived Growth Factor alpha / physiology
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Signal Transduction / drug effects
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Sorafenib
Substances
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Angiogenesis Inhibitors
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Antineoplastic Agents
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Benzenesulfonates
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Neoplasm Proteins
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Phenylurea Compounds
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Protein Kinase Inhibitors
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Pyridines
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Niacinamide
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Sorafenib
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Protein-Tyrosine Kinases
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Receptor, Platelet-Derived Growth Factor alpha