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CC BY 4.0 · Pharmaceutical Fronts 2022; 04(04): e223-e236
DOI: 10.1055/s-0042-1758542
Review Article

Hallmarks of Anaplastic Lymphoma Kinase Inhibitors with Its Quick Emergence of Drug Resistance

Yong-Fu Qiu
1   Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Lian-Hua Song
2   Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, People's Republic of China
,
Gang-Long Jiang
1   Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Zhen Zhang
1   Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
3   School of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai, People's Republic of China
,
Xu-Yan Liu
1   Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Guan Wang
1   Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
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Abstract

Anaplastic lymphoma kinase (ALK) is one of the most popular targets for anticancer therapies. In the past decade, the use of anaplastic lymphoma tyrosine kinase inhibitors (ALK-TKIs), including crizotinib and ceritinib, has been a reliable and standard options for patients with lung cancer, particularly for patients with nonsmall cell lung carcinoma. ALK-targeted therapies initially benefit the patients, yet, resistance eventually occurs. Therefore, resistance mechanisms of ALK-TKIs and the solutions have become a formidable challenge in the development of ALK inhibitors. In this review, based on the knowledge of reported ALK inhibitors, we illustrated the crystal structures of ALK, summarized the resistance mechanisms of ALK-targeted drugs, and proposed potential therapeutic strategies to prevent or overcome the resistance.

Keywords

ALK inhibitors - drug resistance - NSCLC


Publication History

Received: 18 March 2022

Accepted: 30 September 2022

Article published online:
09 December 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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