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Heterogeneity of resistant mechanisms in an EGFR-TKI relapsed patient with EGFR amplification and response to nimotuzumab: A case report

EGFR mutations are the most important drivers of gene alterations in lung adenocarcinomas and are sensitive to EGFR-TKIs. However, resistance to EGFR-TKIs is inevitable in the majority of EGFR-mutated lung cancer patients. Numerous resistant mechanisms have been revealed to date, and more are still...

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Autores principales: Li, Yan, Xu, Ziyi, Xie, Tongji, Xing, Puyuan, Ying, Jianming, Li, Junling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9403890/
https://www.ncbi.nlm.nih.gov/pubmed/36033496
http://dx.doi.org/10.3389/fonc.2022.937282
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author Li, Yan
Xu, Ziyi
Xie, Tongji
Xing, Puyuan
Ying, Jianming
Li, Junling
author_facet Li, Yan
Xu, Ziyi
Xie, Tongji
Xing, Puyuan
Ying, Jianming
Li, Junling
author_sort Li, Yan
collection PubMed
description EGFR mutations are the most important drivers of gene alterations in lung adenocarcinomas and are sensitive to EGFR-TKIs. However, resistance to EGFR-TKIs is inevitable in the majority of EGFR-mutated lung cancer patients. Numerous resistant mechanisms have been revealed to date, and more are still under investigation. Owing to the selective pressure, intratumoral heterogeneity may exist after resistance, especially in patients after multiple lines of treatment. For those patients, it is important to choose therapies focused on the trunk/major clone of the tumor in order to achieve optimal clinical benefit. Here, we will report an EGFR-mutated lung adenocarcinoma patient with heterogeneity of resistant mechanisms including EGFR amplification, large fragment deletion of RB1, and histological transformations after targeted treatments. In our case, EGFR amplification seemed to be the major clone of the resistant mechanism according to the next-generation sequencing (NGS) results of both liquid biopsy monitoring and tissue biopsies. In consideration of the high EGFR amplification level, the patient was administered by combination treatment with EGFR-TKI plus nimotuzumab, an anti-EGFR monoclonal antibody (mAb), and achieved a certain degree of clinical benefit. Our case sheds light on the treatment of EGFR-mutant patients with EGFR amplification and indicates that a combination of EGFR-TKI with anti-EGFR mAb might be one of the possible treatment options based on genetic tests. Moreover, the decision on therapeutic approaches should focus on the major clone of the tumor and should make timely adjustments according to the dynamic changes of genetic characteristics during treatment.
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spelling pubmed-94038902022-08-26 Heterogeneity of resistant mechanisms in an EGFR-TKI relapsed patient with EGFR amplification and response to nimotuzumab: A case report Li, Yan Xu, Ziyi Xie, Tongji Xing, Puyuan Ying, Jianming Li, Junling Front Oncol Oncology EGFR mutations are the most important drivers of gene alterations in lung adenocarcinomas and are sensitive to EGFR-TKIs. However, resistance to EGFR-TKIs is inevitable in the majority of EGFR-mutated lung cancer patients. Numerous resistant mechanisms have been revealed to date, and more are still under investigation. Owing to the selective pressure, intratumoral heterogeneity may exist after resistance, especially in patients after multiple lines of treatment. For those patients, it is important to choose therapies focused on the trunk/major clone of the tumor in order to achieve optimal clinical benefit. Here, we will report an EGFR-mutated lung adenocarcinoma patient with heterogeneity of resistant mechanisms including EGFR amplification, large fragment deletion of RB1, and histological transformations after targeted treatments. In our case, EGFR amplification seemed to be the major clone of the resistant mechanism according to the next-generation sequencing (NGS) results of both liquid biopsy monitoring and tissue biopsies. In consideration of the high EGFR amplification level, the patient was administered by combination treatment with EGFR-TKI plus nimotuzumab, an anti-EGFR monoclonal antibody (mAb), and achieved a certain degree of clinical benefit. Our case sheds light on the treatment of EGFR-mutant patients with EGFR amplification and indicates that a combination of EGFR-TKI with anti-EGFR mAb might be one of the possible treatment options based on genetic tests. Moreover, the decision on therapeutic approaches should focus on the major clone of the tumor and should make timely adjustments according to the dynamic changes of genetic characteristics during treatment. Frontiers Media S.A. 2022-08-11 /pmc/articles/PMC9403890/ /pubmed/36033496 http://dx.doi.org/10.3389/fonc.2022.937282 Text en Copyright © 2022 Li, Xu, Xie, Xing, Ying and Li 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 Oncology
Li, Yan
Xu, Ziyi
Xie, Tongji
Xing, Puyuan
Ying, Jianming
Li, Junling
Heterogeneity of resistant mechanisms in an EGFR-TKI relapsed patient with EGFR amplification and response to nimotuzumab: A case report
title Heterogeneity of resistant mechanisms in an EGFR-TKI relapsed patient with EGFR amplification and response to nimotuzumab: A case report
title_full Heterogeneity of resistant mechanisms in an EGFR-TKI relapsed patient with EGFR amplification and response to nimotuzumab: A case report
title_fullStr Heterogeneity of resistant mechanisms in an EGFR-TKI relapsed patient with EGFR amplification and response to nimotuzumab: A case report
title_full_unstemmed Heterogeneity of resistant mechanisms in an EGFR-TKI relapsed patient with EGFR amplification and response to nimotuzumab: A case report
title_short Heterogeneity of resistant mechanisms in an EGFR-TKI relapsed patient with EGFR amplification and response to nimotuzumab: A case report
title_sort heterogeneity of resistant mechanisms in an egfr-tki relapsed patient with egfr amplification and response to nimotuzumab: a case report
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9403890/
https://www.ncbi.nlm.nih.gov/pubmed/36033496
http://dx.doi.org/10.3389/fonc.2022.937282
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