ArticleMolecular oncology2014
The TPM3-NTRK1 rearrangement is a recurring event in colorectal carcinoma and is associated with tumor sensitivity to TRKA kinase inhibition.
Article in Molecular oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.
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Who cites it
83 citing papers in PubMed, 1 synthesis or guideline pooled it, 152 citations in OpenAlex.
- Distant Metastasis in Colorectal Cancer Patients-Do We Have New Predicting Clinicopathological and Molecular Biomarkers? A Comprehensive Review.International journal of molecular sciences · 2020Pooled it
- Safety and Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK Inhibitor Entrectinib: Combined Results from Two Phase I Trials (ALKA-372-001 and STARTRK-1).Cancer discovery · 2017Trial
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- MiRQuery: a user-friendly web app for the interactive analysis and visualization of microRNA sequencing data.BMC bioinformatics · 2026Article
- Tissue and cellular spatiotemporal dynamics in colon aging.Nature biotechnology · 2026Article
- Tropomyosin 3 Gene Fusions in Cancers: From Mechanisms to Treatments-A Comprehensive Review.Cancer medicine · 2025Review
- TPM3-NTRK1 fusion confers resistance to osimertinib in lung adenocarcinoma: a model in a continuous cell line.Human cell · 2025Article
- Computational studies on structural aspects of pyrazolo[3,4-b]pyridine derivatives as TRKA inhibitors in cancer therapy.Scientific reports · 2025Article
- Article
- The mutual interplay between NTRK fusion genes and human papillomavirus infection in cervical cancer progression (Review).Molecular and clinical oncology · 2024Review
- Review
- Progress in clinical diagnosis and treatment of colorectal cancer with rare genetic variants.Cancer biology & medicine · 2024Review
- Anchored-fusion enables targeted fusion search in bulk and single-cell RNA sequencing data.Cell reports methods · 2024Article
- Perineural invasion in colorectal cancer: mechanisms of action and clinical relevance.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Nerve Growth Factor and the Role of Inflammation in Tumor Development.Current issues in molecular biology · 2024Review
- From genomic spectrum of NTRK genes to adverse effects of its inhibitors, a comprehensive genome-based and real-world pharmacovigilance analysis.Frontiers in pharmacology · 2024Article
- Research Advances in the Role of the Tropomyosin Family in Cancer.International journal of molecular sciences · 2023Review
- Decoding Oncofusions: Unveiling Mechanisms, Clinical Impact, and Prospects for Personalized Cancer Therapies.Cancers · 2023Review
- Article
- A Multi-Omics Overview of Colorectal Cancer to Address Mechanisms of Disease, Metastasis, Patient Disparities and Outcomes.Cancers · 2023Review
23 more citing papers are in PubMed but not listed here.
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Authors and funding
28 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The NTRK1 gene encodes Tropomyosin-related kinase A (TRKA), the high-affinity Nerve Growth Factor Receptor. NTRK1 was originally isolated from a colorectal carcinoma (CRC) sample as component of a somatic rearrangement (TPM3-NTRK1) resulting in expression of the oncogenic chimeric protein TPM3-TRKA, but there has been no subsequent report regarding the relevance of this oncogene in CRC. The KM12 human CRC cell line expresses the chimeric TPM3-TRKA protein and is hypersensitive to TRKA kinase inhibition. We report the detailed characterization of the TPM3-NTRK1 genomic rearrangement in KM12 cells and through a cellular screening approach, the identification of NMS-P626, a novel highly potent and selective TRKA inhibitor. NMS-P626 suppressed TPM3-TRKA phosphorylation and downstream signaling in KM12 cells and showed remarkable antitumor activity in mice bearing KM12 tumors. Finally, using quantitative reverse transcriptase PCR and immunohistochemistry (IHC) we identified the TPM3-NTRK1 rearrangement in a CRC clinical sample, therefore suggesting that this chromosomal translocation is indeed a low frequency recurring event in CRC and that such patients might benefit from therapy with TRKA kinase inhibitors.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.