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Emerging strategies to overcome resistance to third-generation EGFR inhibitors

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机构： [1]Department of Respiratory and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Innovation Center of Nursing Research, Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, 610041, China. [2]Tianfu Jincheng Laboratory, Chengdu, 610041, China. [3]Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, 38163, USA. [4]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu 610041, China. [5]Precision Medicine Key Laboratory of Sichuan Province and Precision Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, China.

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关键词： Epidermal growth factor receptor (EGFR) Drug resistance Inhibitors Structure–activity relationship Tyrosine kinase Cancer

摘要：

Epidermal growth factor receptor (EGFR), the receptor for members of the epidermal growth factor family, regulates cell proliferation and signal transduction; moreover, EGFR is related to the inhibition of tumor cell proliferation, angiogenesis, invasion, metastasis, and apoptosis. Therefore, EGFR has become an important target for the treatment of cancer, including non-small cell lung cancer, head and neck cancer, breast cancer, glioma, cervical cancer, and bladder cancer. First- to third-generation EGFR inhibitors have shown considerable efficacy and have significantly improved disease prognosis. However, most patients develop drug resistance after treatment. The challenge of overcoming intrinsic and acquired resistance in primary and recurrent cancer mediated by EGFR mutations is thus driving the search for alternative strategies in the design of new therapeutic agents. In view of resistance to third-generation inhibitors, understanding the intricate mechanisms of resistance will offer insight for the development of more advanced targeted therapies. In this review, we discuss the molecular mechanisms of resistance to third-generation EGFR inhibitors and review recent strategies for overcoming resistance, new challenges, and future development directions.© 2022. The Author(s).

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出版当年[2022]版：

大类 | 1 区

医学

小类 | 1 区血液学 1 区肿瘤学

最新[2023]版：

大类 | 1 区

医学

小类 | 1 区血液学 1 区肿瘤学

第一作者：

第一作者机构： [1]Department of Respiratory and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Innovation Center of Nursing Research, Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, 610041, China. [2]Tianfu Jincheng Laboratory, Chengdu, 610041, China.

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通讯作者：

通讯机构： [1]Department of Respiratory and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Innovation Center of Nursing Research, Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, 610041, China. [2]Tianfu Jincheng Laboratory, Chengdu, 610041, China. [4]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu 610041, China. [5]Precision Medicine Key Laboratory of Sichuan Province and Precision Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, China.

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