Abstract
In this review, the authors discuss common gain-of-function mutations in the stem cell factor receptor KIT found in mast cell proliferation disorders and summarize the current understanding of the molecular mechanisms by which these transforming mutations may affect KIT structure and function leading to altered downstream signaling and cellular transformation. Drugs targeting KIT have shown mixed success in the treatment of mastocytosis and other hyperproliferative diseases. A brief overview of the most common KIT inhibitors currently used, the reasons for the varied clinical results of such inhibitors and a discussion of potential new strategies are provided.
Keywords:
KIT inhibitors; KIT mutations; KIT signaling; KIT trafficking; Mastocytosis.
Published by Elsevier Inc.
Publication types
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Research Support, N.I.H., Intramural
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Review
MeSH terms
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Bone Marrow / drug effects
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Bone Marrow / metabolism
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Bone Marrow / pathology
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Cell Proliferation
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Exons
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Gene Expression Regulation, Neoplastic*
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Hematologic Neoplasms / diagnosis
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Hematologic Neoplasms / drug therapy
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Hematologic Neoplasms / genetics*
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Hematologic Neoplasms / pathology
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Humans
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Mast Cells / drug effects
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Mast Cells / metabolism*
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Mast Cells / pathology
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Mastocytosis / diagnosis
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Mastocytosis / drug therapy
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Mastocytosis / genetics*
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Mastocytosis / pathology
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Mutation
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Protein Kinase Inhibitors / therapeutic use
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Protein Structure, Tertiary
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Protein Transport
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Proto-Oncogene Proteins c-kit / genetics*
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Proto-Oncogene Proteins c-kit / metabolism
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Signal Transduction / genetics*
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Stem Cell Factor / genetics
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Stem Cell Factor / metabolism
Substances
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Protein Kinase Inhibitors
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Stem Cell Factor
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Proto-Oncogene Proteins c-kit