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Case Report: Heterogeneity of Resistance Mechanisms in Different Lesions Co-Mediate Acquired Resistance to First-Line Icotinib in EGFR Mutant Non-Small Cell Lung Cancer

Epidermal growth factor receptor (EGFR)-activating mutations are major oncogenic mechanisms in non-small cell lung cancer (NSCLC). Most patients with NSCLC with EGFR mutations benefit from targeted therapy with EGFR- tyrosine kinase inhibitors (TKIs). One of the main limitations of targeted therapy...

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Autores principales: Liu, Zhicong, Dong, Hui, Chen, Wenyan, Wang, Bin, Ji, Dongxiang, Zhang, Wei, Shi, Xuefei, Feng, Xueren
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302584/
https://www.ncbi.nlm.nih.gov/pubmed/35872785
http://dx.doi.org/10.3389/fmed.2022.906364
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author Liu, Zhicong
Dong, Hui
Chen, Wenyan
Wang, Bin
Ji, Dongxiang
Zhang, Wei
Shi, Xuefei
Feng, Xueren
author_facet Liu, Zhicong
Dong, Hui
Chen, Wenyan
Wang, Bin
Ji, Dongxiang
Zhang, Wei
Shi, Xuefei
Feng, Xueren
author_sort Liu, Zhicong
collection PubMed
description Epidermal growth factor receptor (EGFR)-activating mutations are major oncogenic mechanisms in non-small cell lung cancer (NSCLC). Most patients with NSCLC with EGFR mutations benefit from targeted therapy with EGFR- tyrosine kinase inhibitors (TKIs). One of the main limitations of targeted therapy is that the tumor response is not durable, with the inevitable development of drug resistance. Previous studies demonstrated that the potential resistance mechanisms are diverse, including the presence of EGFR T790M, MET amplification, mesenchymal transformation, and anaplastic lymphoma kinase (ALK) rearrangement. The patient in our report was diagnosed with stage IA lung adenocarcinoma harboring the EGFR L858R mutation and underwent radical surgery. The patient received icotinib for 12 months after recurrence. Subsequent molecular analysis of the left pleural effusion indicated that LCLAT1-ALK fusion might be an underlying mechanism contributing to the acquired resistance to icotinib. Ensartinib was prescribed, but the lesion in the right lung continued to progress. Hence, a re-biopsy and molecular analysis of lesions in the right lung was performed to solve this problem. In contrast to the left pleural effusion, EGFR exon 20 T790M might have mediated the acquired resistance in lesions in the right lung of this patient. The combination of osimertinib and ensartinib has achieved a rapid partial response until now. The complexity and heterogeneity in our case may provide new insights into the resistance mechanisms of targeted therapy.
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spelling pubmed-93025842022-07-22 Case Report: Heterogeneity of Resistance Mechanisms in Different Lesions Co-Mediate Acquired Resistance to First-Line Icotinib in EGFR Mutant Non-Small Cell Lung Cancer Liu, Zhicong Dong, Hui Chen, Wenyan Wang, Bin Ji, Dongxiang Zhang, Wei Shi, Xuefei Feng, Xueren Front Med (Lausanne) Medicine Epidermal growth factor receptor (EGFR)-activating mutations are major oncogenic mechanisms in non-small cell lung cancer (NSCLC). Most patients with NSCLC with EGFR mutations benefit from targeted therapy with EGFR- tyrosine kinase inhibitors (TKIs). One of the main limitations of targeted therapy is that the tumor response is not durable, with the inevitable development of drug resistance. Previous studies demonstrated that the potential resistance mechanisms are diverse, including the presence of EGFR T790M, MET amplification, mesenchymal transformation, and anaplastic lymphoma kinase (ALK) rearrangement. The patient in our report was diagnosed with stage IA lung adenocarcinoma harboring the EGFR L858R mutation and underwent radical surgery. The patient received icotinib for 12 months after recurrence. Subsequent molecular analysis of the left pleural effusion indicated that LCLAT1-ALK fusion might be an underlying mechanism contributing to the acquired resistance to icotinib. Ensartinib was prescribed, but the lesion in the right lung continued to progress. Hence, a re-biopsy and molecular analysis of lesions in the right lung was performed to solve this problem. In contrast to the left pleural effusion, EGFR exon 20 T790M might have mediated the acquired resistance in lesions in the right lung of this patient. The combination of osimertinib and ensartinib has achieved a rapid partial response until now. The complexity and heterogeneity in our case may provide new insights into the resistance mechanisms of targeted therapy. Frontiers Media S.A. 2022-07-07 /pmc/articles/PMC9302584/ /pubmed/35872785 http://dx.doi.org/10.3389/fmed.2022.906364 Text en Copyright © 2022 Liu, Dong, Chen, Wang, Ji, Zhang, Shi and Feng. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Liu, Zhicong
Dong, Hui
Chen, Wenyan
Wang, Bin
Ji, Dongxiang
Zhang, Wei
Shi, Xuefei
Feng, Xueren
Case Report: Heterogeneity of Resistance Mechanisms in Different Lesions Co-Mediate Acquired Resistance to First-Line Icotinib in EGFR Mutant Non-Small Cell Lung Cancer
title Case Report: Heterogeneity of Resistance Mechanisms in Different Lesions Co-Mediate Acquired Resistance to First-Line Icotinib in EGFR Mutant Non-Small Cell Lung Cancer
title_full Case Report: Heterogeneity of Resistance Mechanisms in Different Lesions Co-Mediate Acquired Resistance to First-Line Icotinib in EGFR Mutant Non-Small Cell Lung Cancer
title_fullStr Case Report: Heterogeneity of Resistance Mechanisms in Different Lesions Co-Mediate Acquired Resistance to First-Line Icotinib in EGFR Mutant Non-Small Cell Lung Cancer
title_full_unstemmed Case Report: Heterogeneity of Resistance Mechanisms in Different Lesions Co-Mediate Acquired Resistance to First-Line Icotinib in EGFR Mutant Non-Small Cell Lung Cancer
title_short Case Report: Heterogeneity of Resistance Mechanisms in Different Lesions Co-Mediate Acquired Resistance to First-Line Icotinib in EGFR Mutant Non-Small Cell Lung Cancer
title_sort case report: heterogeneity of resistance mechanisms in different lesions co-mediate acquired resistance to first-line icotinib in egfr mutant non-small cell lung cancer
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302584/
https://www.ncbi.nlm.nih.gov/pubmed/35872785
http://dx.doi.org/10.3389/fmed.2022.906364
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