MAP2K1 K57N Conferred an Acquired Resistance to Furmonertinib, Dabrafenib and Trametinib Combined Therapy in Advanced Lung Adenocarcinoma with EGFR Mutation and BRAF V600E
{"title":"MAP2K1 K57N Conferred an Acquired Resistance to Furmonertinib, Dabrafenib and Trametinib Combined Therapy in Advanced Lung Adenocarcinoma with EGFR Mutation and BRAF V600E","authors":"Xiang Tan, Zuotao Wu, Mingwu Chen","doi":"10.2147/ott.s454902","DOIUrl":null,"url":null,"abstract":"<strong>Abstract:</strong> Previous case reports have demonstrated the effectiveness of combination therapy involving EGFR TKI, <em>BRAF</em> inhibitor dabrafenib, and <em>MEK</em> inhibitor trametinib in metastatic non-small-cell lung cancer (NSCLC) patients with acquired <em>BRAF</em> V600E and <em>EGFR</em> mutations. However, the current literature does not provide any reports on the presence of resistant mutations in response to the administration of three-drug combination therapy. Exploring the resistance mechanism of targeted therapy is helpful to optimize the subsequent treatment strategy of patients. Herein, we report a case of a patient with advanced <em>EGFR</em> positive lung adenocarcinoma harboring an acquired <em>BRAF</em> V600E mutation who responded to the combination of furmonertinib, dabrafenib, and trametinib therapy. Unexpectedly, a <em>MAP2K1</em> K57N acquired mutation was identified by NGS (Next-generation sequencing) analysis of re-biopsy tumor tissue after the patient was resistant to three-drug therapy. As far as we know, this is the first report demonstrating that the efficacy of using combination of furmonertinib and <em>BRAF</em>/<em>MEK</em> inhibitors and the <em>MAP2K1</em> K57N mutation serves as a resistant mechanism to the three-drug therapy. This novel finding not only revealed a new resistant mutation but also had important implications for the identification of effective patients to EGFR/BRAF/MEK combination therapy.<br/><br/><strong>Keywords:</strong> MAP2K1, furmonertinib, lung adenocarcinoma, EGFR, mutation<br/>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"OncoTargets and therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/ott.s454902","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Abstract: Previous case reports have demonstrated the effectiveness of combination therapy involving EGFR TKI, BRAF inhibitor dabrafenib, and MEK inhibitor trametinib in metastatic non-small-cell lung cancer (NSCLC) patients with acquired BRAF V600E and EGFR mutations. However, the current literature does not provide any reports on the presence of resistant mutations in response to the administration of three-drug combination therapy. Exploring the resistance mechanism of targeted therapy is helpful to optimize the subsequent treatment strategy of patients. Herein, we report a case of a patient with advanced EGFR positive lung adenocarcinoma harboring an acquired BRAF V600E mutation who responded to the combination of furmonertinib, dabrafenib, and trametinib therapy. Unexpectedly, a MAP2K1 K57N acquired mutation was identified by NGS (Next-generation sequencing) analysis of re-biopsy tumor tissue after the patient was resistant to three-drug therapy. As far as we know, this is the first report demonstrating that the efficacy of using combination of furmonertinib and BRAF/MEK inhibitors and the MAP2K1 K57N mutation serves as a resistant mechanism to the three-drug therapy. This novel finding not only revealed a new resistant mutation but also had important implications for the identification of effective patients to EGFR/BRAF/MEK combination therapy.
期刊介绍:
OncoTargets and Therapy is an international, peer-reviewed journal focusing on molecular aspects of cancer research, that is, the molecular diagnosis of and targeted molecular or precision therapy for all types of cancer.
The journal is characterized by the rapid reporting of high-quality original research, basic science, reviews and evaluations, expert opinion and commentary that shed novel insight on a cancer or cancer subtype.
Specific topics covered by the journal include:
-Novel therapeutic targets and innovative agents
-Novel therapeutic regimens for improved benefit and/or decreased side effects
-Early stage clinical trials
Further considerations when submitting to OncoTargets and Therapy:
-Studies containing in vivo animal model data will be considered favorably.
-Tissue microarray analyses will not be considered except in cases where they are supported by comprehensive biological studies involving multiple cell lines.
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-Studies utilizing publicly available data (e.g. GWAS/TCGA/GEO etc.) should add to the body of knowledge about a specific disease or relevant phenotype and must be validated using the authors’ own data through replication in an independent sample set and functional follow-up.
-Bioinformatics studies must be validated using the authors’ own data through replication in an independent sample set and functional follow-up.
-Single nucleotide polymorphism (SNP) studies will not be considered.