Abstract
Cancer therapeutics that target a signaling pathway to which the cancer cells are addicted can deliver dramatic initial responses, but resistance is nearly always inevitable. A variety of mechanisms that cancer cells employ to escape from targeted cancer drugs have been described. We review here the role of Hepatocyte Growth Factor (HGF) and its receptor MET in drug resistance. We present data demonstrating that HGF can confer resistance to a number of kinase inhibitors in a variety of cancer cell lines and discuss our results in relation to the findings of others. Together, these data point at a major role for HGF/MET signaling in resistance to a variety of targeted cancer drugs.
Keywords:
EMT; HGF; MET; drug resistance; targeted therapies.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use
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Drug Resistance, Neoplasm
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ErbB Receptors / genetics
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ErbB Receptors / metabolism
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Hepatocyte Growth Factor / metabolism*
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Humans
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Lung Neoplasms / drug therapy
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Mitogen-Activated Protein Kinases / metabolism
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Protein Kinase Inhibitors / pharmacology
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Protein Kinase Inhibitors / therapeutic use
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Proto-Oncogene Proteins c-akt / metabolism
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Proto-Oncogene Proteins c-met / metabolism*
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Signal Transduction* / drug effects
Substances
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Antineoplastic Agents
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Protein Kinase Inhibitors
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Hepatocyte Growth Factor
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ErbB Receptors
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Proto-Oncogene Proteins c-met
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Proto-Oncogene Proteins c-akt
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Mitogen-Activated Protein Kinases