New targets bring hope in squamous cell lung cancer: neurotrophic tyrosine kinase gene fusions

Laboratory Investigation; a Journal of Technical Methods and Pathology
Christian Rolfo, Luis Raez

Abstract

Neurotrophic tyrosine kinase genes encode for the Trk-family proteins TrkA, TrkB, and TrkC, which have an important role in the development of the nervous system; however, they have been identified as oncogenic fusions in solid tumors (NTK-1, NTRK-2, and NTRK-3) and are associated with poor survival in lung cancer. These three new fusions can be detected by fluorescent in situ hybridization or next-generation sequencing in less than 5% of the lung tumors. There are several ongoing clinical trials of NTRK oncogenes in lung cancer and other tumors. The agents entrectinib (RXDX-101), a multi-kinase small molecule inhibitor that selectively inhibits NTRK1, NTRK2, and NTRK3, ROS1 and ALK, and LOXO-101, an ATP-competitive pan-NTRK inhibitor, have shown responses in patients with lung cancer with an acceptable toxicity profile. Although these oncogenic fusions are not very prevalent, the high prevalence of lung cancer makes these findings very relevant and suggests the feasibility of these oncogenes as targets in lung cancer. New data from Ozono and collaborators presented in this issue suggest that BDNF/TrkB signal promotes proliferating migratory and invasive phenotypes and cellular plasticity in squamous cell carcinoma (SCC) of the...Continue Reading

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Jun 13, 2017·Laboratory Investigation; a Journal of Technical Methods and Pathology·Keigo OzonoYoshinao Oda

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Citations

May 1, 2020·Veterinary Pathology·Bernadette RogezXuefen Le Bourhis
Sep 2, 2018·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Zoran GatalicaSemir Vranic
Feb 15, 2019·FEBS Open Bio·Zhi-Peng RenXiang-Yang Chu
May 30, 2020·International Journal of Molecular Sciences·Federica Zito MarinoRenato Franco
Sep 11, 2020·Cytokine·Vilson Serafim JuniorEny Maria Goloni-Bertollo

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