Current Therapeutic Strategies and Prospects for EGFR Mutation-Positive Lung Cancer Based on the Mechanisms Underlying Drug Resistance

The discovery of activating mutations in the epidermal growth factor receptor (<i>EGFR</i>) gene and the development of EGFR tyrosine kinase inhibitors (TKIs) have led to a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). <i>EGFR</i> mutation-positive NS...

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Autores principales:	Yukari Tsubata, Ryosuke Tanino, Takeshi Isobe
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	epidermal growth factor receptor gene mutation epidermal growth factor receptor-tyrosine kinase inhibitor acquired resistance pemetrexed targeted therapy Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/5cfa5435b6c34b2f8549d7967e087ca1
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spelling	oai:doaj.org-article:5cfa5435b6c34b2f8549d7967e087ca12021-11-25T17:12:41ZCurrent Therapeutic Strategies and Prospects for EGFR Mutation-Positive Lung Cancer Based on the Mechanisms Underlying Drug Resistance10.3390/cells101131922073-4409https://doaj.org/article/5cfa5435b6c34b2f8549d7967e087ca12021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3192https://doaj.org/toc/2073-4409The discovery of activating mutations in the epidermal growth factor receptor (<i>EGFR</i>) gene and the development of EGFR tyrosine kinase inhibitors (TKIs) have led to a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). <i>EGFR</i> mutation-positive NSCLC is common in East Asia, and approximately 50% of adenocarcinomas harbor <i>EGFR</i> mutations. Undoubtedly, EGFR-TKIs, with their promising efficacy, are the mainstay of primary therapy. However, even if tumor shrinkage is achieved, most patients become resistant to EGFR-TKIs and relapse; hence, EGFR-TKIs do not achieve a radical cure. The problem of the development of resistance to targeted drugs has been a persistent challenge. After the role of <i>EGFR</i> T790M mutation in acquired drug resistance was reported, osimertinib, a third-generation irreversible EGFR-TKI, was designed to overcome the resistance conferred by T790M mutation. In addition, some studies have reported the mechanism of drug resistance caused by mutations other than the T790M mutation and strategies to overcome them. Elucidating the mechanism underlying drug resistance development and combining therapeutic approaches are expected to further improve NSCLC prognosis.Yukari TsubataRyosuke TaninoTakeshi IsobeMDPI AGarticleepidermal growth factor receptor gene mutationepidermal growth factor receptor-tyrosine kinase inhibitoracquired resistancepemetrexedtargeted therapyBiology (General)QH301-705.5ENCells, Vol 10, Iss 3192, p 3192 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	epidermal growth factor receptor gene mutation epidermal growth factor receptor-tyrosine kinase inhibitor acquired resistance pemetrexed targeted therapy Biology (General) QH301-705.5
spellingShingle	epidermal growth factor receptor gene mutation epidermal growth factor receptor-tyrosine kinase inhibitor acquired resistance pemetrexed targeted therapy Biology (General) QH301-705.5 Yukari Tsubata Ryosuke Tanino Takeshi Isobe Current Therapeutic Strategies and Prospects for EGFR Mutation-Positive Lung Cancer Based on the Mechanisms Underlying Drug Resistance
description	The discovery of activating mutations in the epidermal growth factor receptor (<i>EGFR</i>) gene and the development of EGFR tyrosine kinase inhibitors (TKIs) have led to a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). <i>EGFR</i> mutation-positive NSCLC is common in East Asia, and approximately 50% of adenocarcinomas harbor <i>EGFR</i> mutations. Undoubtedly, EGFR-TKIs, with their promising efficacy, are the mainstay of primary therapy. However, even if tumor shrinkage is achieved, most patients become resistant to EGFR-TKIs and relapse; hence, EGFR-TKIs do not achieve a radical cure. The problem of the development of resistance to targeted drugs has been a persistent challenge. After the role of <i>EGFR</i> T790M mutation in acquired drug resistance was reported, osimertinib, a third-generation irreversible EGFR-TKI, was designed to overcome the resistance conferred by T790M mutation. In addition, some studies have reported the mechanism of drug resistance caused by mutations other than the T790M mutation and strategies to overcome them. Elucidating the mechanism underlying drug resistance development and combining therapeutic approaches are expected to further improve NSCLC prognosis.
format	article
author	Yukari Tsubata Ryosuke Tanino Takeshi Isobe
author_facet	Yukari Tsubata Ryosuke Tanino Takeshi Isobe
author_sort	Yukari Tsubata
title	Current Therapeutic Strategies and Prospects for EGFR Mutation-Positive Lung Cancer Based on the Mechanisms Underlying Drug Resistance
title_short	Current Therapeutic Strategies and Prospects for EGFR Mutation-Positive Lung Cancer Based on the Mechanisms Underlying Drug Resistance
title_full	Current Therapeutic Strategies and Prospects for EGFR Mutation-Positive Lung Cancer Based on the Mechanisms Underlying Drug Resistance
title_fullStr	Current Therapeutic Strategies and Prospects for EGFR Mutation-Positive Lung Cancer Based on the Mechanisms Underlying Drug Resistance
title_full_unstemmed	Current Therapeutic Strategies and Prospects for EGFR Mutation-Positive Lung Cancer Based on the Mechanisms Underlying Drug Resistance
title_sort	current therapeutic strategies and prospects for egfr mutation-positive lung cancer based on the mechanisms underlying drug resistance
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/5cfa5435b6c34b2f8549d7967e087ca1
work_keys_str_mv	AT yukaritsubata currenttherapeuticstrategiesandprospectsforegfrmutationpositivelungcancerbasedonthemechanismsunderlyingdrugresistance AT ryosuketanino currenttherapeuticstrategiesandprospectsforegfrmutationpositivelungcancerbasedonthemechanismsunderlyingdrugresistance AT takeshiisobe currenttherapeuticstrategiesandprospectsforegfrmutationpositivelungcancerbasedonthemechanismsunderlyingdrugresistance
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Current Therapeutic Strategies and Prospects for EGFR Mutation-Positive Lung Cancer Based on the Mechanisms Underlying Drug Resistance

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