Oncotarget

Reviews:

Mechanisms of resistance to irreversible epidermal growth factor receptor tyrosine kinase inhibitors and therapeutic strategies in non-small cell lung cancer

Jing Xu, Jinghui Wang and Shucai Zhang _

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Oncotarget. 2017; 8:90557-90578. https://doi.org/10.18632/oncotarget.21164

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Abstract

Jing Xu1, Jinghui Wang1 and Shucai Zhang1

1Department of Medical Oncology, Beijing Tuberculosis and Thoracic Tumor Research Institute/Beijing Chest Hospital, Capital Medical University, Beijing, China

Correspondence to:

Shucai Zhang, email: sczhang6304@163.com

Keywords: NSCLC, irreversible EGFR-TKIs, resistance, mechanisms, therapeutic strategies

Received: June 16, 2017     Accepted: August 28, 2017     Published: September 22, 2017

ABSTRACT

Epidermal growth factor receptor (EGFR) T790M mutation is the most frequent mechanism which accounts for about 60% of acquired resistance to first-generation EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) patients harboring EGFR activating mutations. Irreversible EGFR-TKIs which include the second-generation and third-generation EGFR-TKIs are developed to overcome T790M mediated resistance. The second-generation EGFR-TKIs inhibit the wide type (WT) EGFR combined with dose-limiting toxicity which limits its application in clinics, while the development of third-generation EGFR-TKIs brings inspiring efficacy either in vitro or in vivo. The acquired resistance, however, will also occur and limit their response. Understanding the mechanisms of resistance to irreversible EGFR-TKIs plays an important role in the choice of subsequent treatment. In this review, we show the currently known mechanisms of resistance which can be summarized as EGFR dependent and independent mechanisms and potential therapeutic strategies to irreversible EGFR-TKIs.


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