ALK rearranged non–small cell lung carcinoma with EML4-NTRK3 fusion as a possible mechanism of resistance to third-generation ALK inhibitors

Objectives: Neurotrophic tropomyosin receptor kinase (NTRK) fusions might be an off-target resistance mechanism to ALK Tyrosine Kinase Inhibitors (TKIs) in the same way as it has been suggested with activating epidermal growth factor receptor (EGFR) TKIs. Materials and methods: DNA and RNA next-gene...

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Autores principales:	Elena Corral de la Fuente, Amparo Benito Berlinches, Ana Gomez Rueda, María Eugenia Olmedo García, Yolanda Lage Alfranca, Margaret Lario, Almudena Santón Roldán, Pilar Garrido
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Non-small cell lung cancer ALK fusion NTRK3 fusion ALK TKI resistance Next generation sequencing Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/5880d69d21dd4dc1b807fb5ddf5f7f20
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spelling	oai:doaj.org-article:5880d69d21dd4dc1b807fb5ddf5f7f202021-11-04T04:42:16ZALK rearranged non–small cell lung carcinoma with EML4-NTRK3 fusion as a possible mechanism of resistance to third-generation ALK inhibitors2666-621910.1016/j.cpccr.2021.100124https://doaj.org/article/5880d69d21dd4dc1b807fb5ddf5f7f202021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2666621921000727https://doaj.org/toc/2666-6219Objectives: Neurotrophic tropomyosin receptor kinase (NTRK) fusions might be an off-target resistance mechanism to ALK Tyrosine Kinase Inhibitors (TKIs) in the same way as it has been suggested with activating epidermal growth factor receptor (EGFR) TKIs. Materials and methods: DNA and RNA next-generation sequencing (NGS) was performed on the resected brain metastasis of a patient with advanced ALK Rearranged Non–Small Cell Lung Carcinoma (NSCLC) after resistance to several ALK TKIs including third generation ALK inhibitor, for pathological diagnosis and molecular resistance mechanism analysis. Results and conclusion: NGS revealed an EML4-NTRK3 fusion that was confirmed by Immunohistochemistry (IHC) and Fluorescence in situ hybridization (FISH). Despite having two potential targetable fusions, the patient did not respond to entrectinib, a multi-targeted pan-RTK, ROS1 and ALK inhibitor. NGS: analysis in blood or tissues samples should be encouraged once resistance develops to TKIs in patients with ALK rearrangements, as actionable fusions, mutations or amplifications might arise as resistance mechanism and some patients could benefit from targeted therapy.Elena Corral de la FuenteAmparo Benito BerlinchesAna Gomez RuedaMaría Eugenia Olmedo GarcíaYolanda Lage AlfrancaMargaret LarioAlmudena Santón RoldánPilar GarridoElsevierarticleNon-small cell lung cancerALK fusionNTRK3 fusionALK TKI resistanceNext generation sequencingNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCurrent Problems in Cancer: Case Reports, Vol 4, Iss , Pp 100124- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Non-small cell lung cancer ALK fusion NTRK3 fusion ALK TKI resistance Next generation sequencing Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Non-small cell lung cancer ALK fusion NTRK3 fusion ALK TKI resistance Next generation sequencing Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Elena Corral de la Fuente Amparo Benito Berlinches Ana Gomez Rueda María Eugenia Olmedo García Yolanda Lage Alfranca Margaret Lario Almudena Santón Roldán Pilar Garrido ALK rearranged non–small cell lung carcinoma with EML4-NTRK3 fusion as a possible mechanism of resistance to third-generation ALK inhibitors
description	Objectives: Neurotrophic tropomyosin receptor kinase (NTRK) fusions might be an off-target resistance mechanism to ALK Tyrosine Kinase Inhibitors (TKIs) in the same way as it has been suggested with activating epidermal growth factor receptor (EGFR) TKIs. Materials and methods: DNA and RNA next-generation sequencing (NGS) was performed on the resected brain metastasis of a patient with advanced ALK Rearranged Non–Small Cell Lung Carcinoma (NSCLC) after resistance to several ALK TKIs including third generation ALK inhibitor, for pathological diagnosis and molecular resistance mechanism analysis. Results and conclusion: NGS revealed an EML4-NTRK3 fusion that was confirmed by Immunohistochemistry (IHC) and Fluorescence in situ hybridization (FISH). Despite having two potential targetable fusions, the patient did not respond to entrectinib, a multi-targeted pan-RTK, ROS1 and ALK inhibitor. NGS: analysis in blood or tissues samples should be encouraged once resistance develops to TKIs in patients with ALK rearrangements, as actionable fusions, mutations or amplifications might arise as resistance mechanism and some patients could benefit from targeted therapy.
format	article
author	Elena Corral de la Fuente Amparo Benito Berlinches Ana Gomez Rueda María Eugenia Olmedo García Yolanda Lage Alfranca Margaret Lario Almudena Santón Roldán Pilar Garrido
author_facet	Elena Corral de la Fuente Amparo Benito Berlinches Ana Gomez Rueda María Eugenia Olmedo García Yolanda Lage Alfranca Margaret Lario Almudena Santón Roldán Pilar Garrido
author_sort	Elena Corral de la Fuente
title	ALK rearranged non–small cell lung carcinoma with EML4-NTRK3 fusion as a possible mechanism of resistance to third-generation ALK inhibitors
title_short	ALK rearranged non–small cell lung carcinoma with EML4-NTRK3 fusion as a possible mechanism of resistance to third-generation ALK inhibitors
title_full	ALK rearranged non–small cell lung carcinoma with EML4-NTRK3 fusion as a possible mechanism of resistance to third-generation ALK inhibitors
title_fullStr	ALK rearranged non–small cell lung carcinoma with EML4-NTRK3 fusion as a possible mechanism of resistance to third-generation ALK inhibitors
title_full_unstemmed	ALK rearranged non–small cell lung carcinoma with EML4-NTRK3 fusion as a possible mechanism of resistance to third-generation ALK inhibitors
title_sort	alk rearranged non–small cell lung carcinoma with eml4-ntrk3 fusion as a possible mechanism of resistance to third-generation alk inhibitors
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/5880d69d21dd4dc1b807fb5ddf5f7f20
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ALK rearranged non–small cell lung carcinoma with EML4-NTRK3 fusion as a possible mechanism of resistance to third-generation ALK inhibitors

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