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Tropomyosin receptor kinases in sarcomas – of joy and despair
Current Opinion in Oncology, 2021Purpose of review The relatively recent discovery of neurotrophic tropomyosin receptor kinase (NTRK) gene arrangements as pan-tumor predictive biomarkers has led to impressive novel treatments for patients with TRK fusions. Although the number of patients who qualify for treatment is vanishingly small for cancer patients in ...
Sebastian Bauer +2 more
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Future Oncology, 2020
Gene fusions involving NTRK1, NTRK2 and NTRK3 are oncogenic drivers across a wide variety of cancer types. Inhibitors of the chimeric TRKA/B/C protein kinases encoded by these fusions are now available, including larotrectinib, a potent and highly selective oral drug.
Anna F Farago, George D Demetri
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Gene fusions involving NTRK1, NTRK2 and NTRK3 are oncogenic drivers across a wide variety of cancer types. Inhibitors of the chimeric TRKA/B/C protein kinases encoded by these fusions are now available, including larotrectinib, a potent and highly selective oral drug.
Anna F Farago, George D Demetri
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Targeting tropomyosin receptor kinase for cancer therapy
European Journal of Medicinal Chemistry, 2019NTRKs and their expression product tropomyosin receptor kinases (Trks) are widely distributed in mammals. While neural growth factor (NGF)-induced normal Trk activation plays a key role in nerve growth, NTRK alternations occurring in tumor cells were highly correlated to tumor progression and invasion.
Qi Miao +4 more
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Tropomyosin receptor kinase inhibitors: an updated patent review for 2016–2019
Expert Opinion on Therapeutic Patents, 2020Introduction: Tropomyosin receptor kinases (Trks) control processes in the fields of growth, survival, and differentiation of neuronal processes. They also play a crucial role in neurodegenerative diseases as well as different types of cancer. Interest in developing Trk inhibitors to target NTRK fusion-driven cancers has escalated in the last decade ...
Carolin Jaworski +5 more
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Diagnosis and Management of Tropomyosin Receptor Kinase Fusion-Positive Thyroid Carcinomas
JAMA Oncology, 2023ImportanceThyroid epithelial malignant neoplasms include differentiated thyroid carcinomas (papillary, follicular, and oncocytic), follicular-derived high-grade thyroid carcinomas, and anaplastic and medullary thyroid carcinomas, with additional rarer subtypes.
Haddad, Robert +11 more
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Discovery of First-In-Class Potent and Selective Tropomyosin Receptor Kinase Degraders
Journal of Medicinal Chemistry, 2020We report compounds 5 (CG416) and 6 (CG428) as two first-in-class tropomyosin receptor kinase (TRK) degraders that target the intracellular kinase domain of TRK. Degraders 5 and 6 reduced levels of the tropomyosin 3 (TPM3)-TRKA fusion protein in KM12 colorectal carcinoma cells and inhibited downstream PLCγ1 signaling at sub-nanomolar concentrations ...
Liqun Chen +16 more
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Tropomyosin receptor kinase inhibitors: a patent update 2009 – 2013
Expert Opinion on Therapeutic Patents, 2014Tropomyosin receptor kinases (Trks) are a family of three similar tyrosine kinases activated by peptide hormones of the neurotrophin family. The nerve growth factor antibody tanezumab has provided clinical proof of concept for inhibition of the TrkA pathway in pain.
Edward Walker, Clive Mccarthy
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Neurological Sciences, 2023
Parkinson's disease is a complex age-related progressive dopaminergic neurodegenerative disease consistently viewed as a disorder of movement and is characterized by its cardinal motor symptoms. While the motor symptoms and its clinical manifestations are attributed to the nigral dopaminergic neuronal death and basal ganglia dysfunction, studies have ...
Jeyaram Bharathi J +7 more
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Parkinson's disease is a complex age-related progressive dopaminergic neurodegenerative disease consistently viewed as a disorder of movement and is characterized by its cardinal motor symptoms. While the motor symptoms and its clinical manifestations are attributed to the nigral dopaminergic neuronal death and basal ganglia dysfunction, studies have ...
Jeyaram Bharathi J +7 more
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An isoform-selective inhibitor of tropomyosin receptor kinase A behaves as molecular glue
Bioorganic & Medicinal Chemistry Letters, 2020The production of TrkA-selective inhibitors is considerably difficult because the kinase domains of TrkA and its isoforms TrkB/C have highly homologous amino acid sequences. Here we describe the structural basis for the acquisition of selectivity for a isoform-selective TrkA inhibitor, namely compound V1.
Noritaka Furuya +8 more
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Identification of tropomyosin kinase receptor (TRK) mutations in cancer.
Journal of Clinical Oncology, 20151553 Background: TRK A, B and C, (encoded by NTRK1, NTRK2, and NTRK3 genes, respectively) and their neurotrophin ligands regulate growth, differentiation and survival of neurons.
Nisha Nanda +2 more
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