Abstract
The use of kinase-directed precision medicine has been heavily pursued since the discovery and development of imatinib. Annually, it is estimated that around ∼20 000 new cases of tropomyosin receptor kinase (TRK) cancers are diagnosed, with the majority of cases exhibiting a TRK genomic rearrangement. In this Perspective, we discuss current development and clinical applications for TRK precision medicine by providing the following: (1) the biological background and significance of the TRK kinase family, (2) a compilation of known TRK inhibitors and analysis of their cocrystal structures, (3) an overview of TRK clinical trials, and (4) future perspectives for drug discovery and development of TRK inhibitors.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Antineoplastic Agents / metabolism
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use*
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Catalytic Domain
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Cell Line, Tumor
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Drug Discovery
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Humans
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Mice, Inbred BALB C
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Neoplasms / drug therapy*
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Precision Medicine / methods
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Protein Kinase Inhibitors / metabolism
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Protein Kinase Inhibitors / pharmacology
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Protein Kinase Inhibitors / therapeutic use*
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Rats, Sprague-Dawley
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Receptor, trkA / antagonists & inhibitors*
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Receptor, trkA / chemistry
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Receptor, trkA / metabolism
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Receptor, trkB / antagonists & inhibitors*
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Receptor, trkB / chemistry
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Receptor, trkB / metabolism
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Receptor, trkC / antagonists & inhibitors*
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Receptor, trkC / chemistry
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Receptor, trkC / metabolism
Substances
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Antineoplastic Agents
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Protein Kinase Inhibitors
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Receptor, trkA
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Receptor, trkB
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Receptor, trkC