Managing Acquired Resistance to Third-Generation EGFR Tyrosine Kinase Inhibitors Through Co-Targeting MEK/ERK Signaling

Danlei Yu,1,2,* Wen Zhao,2,3,* Karin A Vallega,2 Shi-Yong Sun2 1Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Hematology and Medical Oncology, Emory University School of Medicine and Winship Cancer...

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Autores principales:	Yu D, Zhao W, Vallega KA, Sun SY
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	acquired resistance egfr inhibitors osimertinib mek/erk lung cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/1982d73e2f984aebb1cd7e78aa162755
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spelling	oai:doaj.org-article:1982d73e2f984aebb1cd7e78aa1627552021-12-02T13:30:38ZManaging Acquired Resistance to Third-Generation EGFR Tyrosine Kinase Inhibitors Through Co-Targeting MEK/ERK Signaling1179-2728https://doaj.org/article/1982d73e2f984aebb1cd7e78aa1627552021-02-01T00:00:00Zhttps://www.dovepress.com/managing-acquired-resistance-to-third-generation-egfr-tyrosine-kinase--peer-reviewed-article-LCTThttps://doaj.org/toc/1179-2728Danlei Yu,1,2,* Wen Zhao,2,3,* Karin A Vallega,2 Shi-Yong Sun2 1Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Hematology and Medical Oncology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA, USA; 3Department of Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shi-Yong SunDepartment of Hematology and Medical Oncology, Emory University School of Medicine and Winship Cancer Institute, 1365-C Clifton Road, C3088, Atlanta, GA, 30322, USATel +1 (404) 778-2170Fax +1 (404) 778-5520Email ssun@emory.eduAbstract: Although epidermal growth factor receptor (EGFR)-targeted therapy has improved clinical outcomes of patients with advanced non-small-cell lung cancer (NSCLC) carrying activating EGFR mutations, the development of acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs), including the promising third-generation ones, results in disease progression and has become an unavoidable problem that limits patient long-term benefit. The third-generation EGFR-TKIs, osimertinib and almonertinib, are now approved for the treatment of advanced NSCLC patients harboring activating EGFR mutations (first-line) and/or the resistant T790M mutation (second-line). Clinically, appropriate management of acquired resistance to third-generation EGFR-TKIs will substantially improve their long-term efficacy against EGFR-mutant NSCLC. Recent preclinical and clinical studies suggest that activation of the Ras/Raf/MEK/ERK signaling pathway may be an important resistance mechanism and accordingly co-targeting this pathway effectively overcomes and abrogates acquired resistance to third-generation EGFR-TKIs. This review focuses on discussing the scientific rationale for and potential of co-targeting MEK/ERK signaling in delaying and overcoming acquired resistance to third-generation EGFR-TKIs, particularly osimertinib.Keywords: acquired resistance, EGFR inhibitors, osimertinib, MEK/ERK, lung cancerYu DZhao WVallega KASun SYDove Medical Pressarticleacquired resistanceegfr inhibitorsosimertinibmek/erklung cancerNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENLung Cancer: Targets and Therapy, Vol Volume 12, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	acquired resistance egfr inhibitors osimertinib mek/erk lung cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	acquired resistance egfr inhibitors osimertinib mek/erk lung cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Yu D Zhao W Vallega KA Sun SY Managing Acquired Resistance to Third-Generation EGFR Tyrosine Kinase Inhibitors Through Co-Targeting MEK/ERK Signaling
description	Danlei Yu,1,2,* Wen Zhao,2,3,* Karin A Vallega,2 Shi-Yong Sun2 1Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Hematology and Medical Oncology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA, USA; 3Department of Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shi-Yong SunDepartment of Hematology and Medical Oncology, Emory University School of Medicine and Winship Cancer Institute, 1365-C Clifton Road, C3088, Atlanta, GA, 30322, USATel +1 (404) 778-2170Fax +1 (404) 778-5520Email ssun@emory.eduAbstract: Although epidermal growth factor receptor (EGFR)-targeted therapy has improved clinical outcomes of patients with advanced non-small-cell lung cancer (NSCLC) carrying activating EGFR mutations, the development of acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs), including the promising third-generation ones, results in disease progression and has become an unavoidable problem that limits patient long-term benefit. The third-generation EGFR-TKIs, osimertinib and almonertinib, are now approved for the treatment of advanced NSCLC patients harboring activating EGFR mutations (first-line) and/or the resistant T790M mutation (second-line). Clinically, appropriate management of acquired resistance to third-generation EGFR-TKIs will substantially improve their long-term efficacy against EGFR-mutant NSCLC. Recent preclinical and clinical studies suggest that activation of the Ras/Raf/MEK/ERK signaling pathway may be an important resistance mechanism and accordingly co-targeting this pathway effectively overcomes and abrogates acquired resistance to third-generation EGFR-TKIs. This review focuses on discussing the scientific rationale for and potential of co-targeting MEK/ERK signaling in delaying and overcoming acquired resistance to third-generation EGFR-TKIs, particularly osimertinib.Keywords: acquired resistance, EGFR inhibitors, osimertinib, MEK/ERK, lung cancer
format	article
author	Yu D Zhao W Vallega KA Sun SY
author_facet	Yu D Zhao W Vallega KA Sun SY
author_sort	Yu D
title	Managing Acquired Resistance to Third-Generation EGFR Tyrosine Kinase Inhibitors Through Co-Targeting MEK/ERK Signaling
title_short	Managing Acquired Resistance to Third-Generation EGFR Tyrosine Kinase Inhibitors Through Co-Targeting MEK/ERK Signaling
title_full	Managing Acquired Resistance to Third-Generation EGFR Tyrosine Kinase Inhibitors Through Co-Targeting MEK/ERK Signaling
title_fullStr	Managing Acquired Resistance to Third-Generation EGFR Tyrosine Kinase Inhibitors Through Co-Targeting MEK/ERK Signaling
title_full_unstemmed	Managing Acquired Resistance to Third-Generation EGFR Tyrosine Kinase Inhibitors Through Co-Targeting MEK/ERK Signaling
title_sort	managing acquired resistance to third-generation egfr tyrosine kinase inhibitors through co-targeting mek/erk signaling
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/1982d73e2f984aebb1cd7e78aa162755
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Managing Acquired Resistance to Third-Generation EGFR Tyrosine Kinase Inhibitors Through Co-Targeting MEK/ERK Signaling

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