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ALK, ROS1, TrkA, TrkB, TrkC

Target
ALK, ROS1, TrkA, TrkB, TrkC
Molecular classification
Receptor, Enzyme (specifically, receptor tyrosine kinase), Neurotrophin receptor family (TRK)
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Overview

ALK, ROS1, TrkA, TrkB, and TrkC are all receptor tyrosine kinases considered therapeutic targets in oncology, particularly for cancers driven by gene fusions or aberrant activation. These targets represent distinct proteins from two main families: - Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase involved in nervous system development and is frequently altered in cancers by gene fusions, mutations, or overexpression. - Proto-oncogene tyrosine-protein kinase ROS1 (ROS1) is another receptor tyrosine kinase with roles in cell differentiation and proliferation; it is implicated in several cancers via gene rearrangements. - TrkA, TrkB, and TrkC are members of the tropomyosin receptor kinase (TRK) family, encoded by the NTRK1, NTRK2, and NTRK3 genes, respectively. They bind specific neurotrophins, triggering cell survival, differentiation, and proliferation signals. ALK, ROS1, TrkA, TrkB, and TrkC are receptor tyrosine kinases serving critical roles in signal transduction pathways that govern cell survival, proliferation, and neuronal differentiation. Aberrant activation through genetic fusions or mutations is implicated in various cancers, making these proteins prime therapeutic targets for small molecule kinase inhibitors. Clinically validated drugs target these kinases in multiple solid tumors, and ongoing research continues to address resistance and safety challenges.

Other names
Anaplastic lymphoma kinaseProto-oncogene tyrosine-protein kinase ROS1Tropomyosin receptor kinase ATropomyosin receptor kinase BTropomyosin receptor kinase CNTRK1NTRK2NTRK3
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Mechanism of action

Small molecule inhibitors block kinase activity, preventing autophosphorylation and stopping downstream signaling pathways associated with cell proliferation and survival.

03

Biological functions

Signal transductionCell proliferationCell survivalNeuronal development and differentiationApoptosis
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Disease associations

Cancer (non–small cell lung cancer, sarcomas, pediatric tumors, cholangiocarcinoma, inflammatory myofibroblastic tumor, etc.)Neurodegenerative disease
05

Safety considerations

Development of resistance (solvent-front mutations in kinase domains)Off-target toxicity due to inhibition of related kinasesNeurologic effects, especially for Trk inhibition (altered neurotrophic signaling)Potential cardiotoxicity, liver enzyme elevations, and other adverse effects characteristic of kinase inhibitors
06

Interacting drugs

Entrectinib

3 more in the full profile.

07

Biomarkers

Gene fusions (e.g., EML4-ALK, CD74-ROS1, NTRK1/2/3 rearrangements)Immunohistochemistry (TRK protein detection)Phosphorylation status of the target receptors (monitoring efficacy of kinase inhibitors)

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