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Πέμπτη 21 Ιουνίου 2018

Celastrol improves the therapeutic efficacy of EGFR-TKIs for non-small-cell lung cancer by overcoming EGFR T790M drug resistance

The development of resistance to therapy continues to be a serious clinical problem in lung cancer management. Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is one of the most common chemotherapy drugs to treat non-small-cell lung cancer. However, almost all treatments fail after ∼1 year of treatment because of drug tolerance, probably occurring from the threonine 790 mutation (T790M) of the EGFR, resulting in overactivation of the EGFR. Celastrol is a natural compound that exhibits antiproliferative activity. In this study, we showed that celastrol combined with EGFR-TKIs significantly suppressed cell invasion of lung cancer cells with a T790M mutation by suppressing the EGFR pathway. Combined therapy with celastrol and EGFR-TKIs inhibited tumor growth in vivo. Together, these results suggested that combined therapy with EGFR-TKIs and celastrol may be a more effective treatment of patients with non-small-cell lung cancer with T790M mutations of the EGFR. * Ying Wang and Qiuyun Liu contributed equally to this article. Correspondence to Denghai Zhang, MD and Limin Xu, DSc, Sino-French Cooperative Central Lab, Shanghai Gongli Hospital, 219 Miao Pu Road, Pudong New District, Shanghai 200135, China Tel: +86 021 5885 9398; fax: +86 021 3882 1635; e-mails: shanghai_zhang@163.com; 13564378807@163.com Received December 22, 2017 Accepted April 24, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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