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作 者:Jia Zhong Hua Bai Zhijie Wang Jianchun Duan Wei Zhuang Di Wang Rui Wan Jiachen Xu Kailun Fei Zixiao Ma Xue Zhang Jie Wang
出 处:《Frontiers of Medicine》2023年第1期18-42,共25页医学前沿(英文版)
基 金:Beijing Natural Science Foundation(No.7222144);National Key Research and Development Project(No.2019YFC1315700);CAMS Key Laboratory of Translational Research on Lung Cancer(No.2018PT31035).
摘 要:With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations (“target-dependent resistance”) and in the parallel and downstream pathways (“target-independent resistance”). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.
关 键 词:non-small cell lung cancer driver mutations treatment strategy resistant mechanism immune-checkpoint inhibitors
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