Abstract
Progression on first-line therapy with imatinib in gastrointestinal stromal tumors (GIST) is caused by either initial resistance or more often a secondary mutation in tyrosine kinases KIT or PDGFR. Therapies in development for imatinib-resistant GIST include agents that target KIT/PDGFR with greater potency or possess broader kinase inhibition profiles including VEGFR. To circumvent secondary mutations in KIT/PDGFR, inhibition of the downstream signaling in PI3K/Akt/mTOR pathway and enhanced degradation of KIT/PDGFR are also under investigation.
Copyright © 2011 Wiley Periodicals, Inc.
MeSH terms
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Antineoplastic Agents / therapeutic use*
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Benzamides
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Gastrointestinal Neoplasms / drug therapy*
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Gastrointestinal Neoplasms / genetics
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Gastrointestinal Stromal Tumors / drug therapy*
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Gastrointestinal Stromal Tumors / genetics
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Humans
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Imatinib Mesylate
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Indoles / therapeutic use
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Mutation
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Piperazines / therapeutic use*
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Piperidines
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Proto-Oncogene Proteins c-kit / genetics
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Pyridines
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Pyrimidines / therapeutic use*
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Pyrroles / therapeutic use
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Receptors, Platelet-Derived Growth Factor / genetics
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Sunitinib
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Thiazoles / therapeutic use
Substances
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Antineoplastic Agents
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Benzamides
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Indoles
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Piperazines
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Piperidines
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Pyridines
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Pyrimidines
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Pyrroles
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Thiazoles
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Imatinib Mesylate
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Proto-Oncogene Proteins c-kit
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Receptors, Platelet-Derived Growth Factor
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nilotinib
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masitinib
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Sunitinib