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Review
. 2023 Feb;17(1):18-42.
doi: 10.1007/s11684-022-0976-4. Epub 2023 Feb 23.

Treatment of advanced non-small cell lung cancer with driver mutations: current applications and future directions

Jia Zhong  1 , Hua Bai  1 , Zhijie Wang  1 , Jianchun Duan  1 , Wei Zhuang  1 , Di Wang  1 , Rui Wan  1 , Jiachen Xu  1 , Kailun Fei  1 , Zixiao Ma  1 , Xue Zhang  1 , Jie Wang  2
Affiliations
Review

Treatment of advanced non-small cell lung cancer with driver mutations: current applications and future directions

Jia Zhong et al. Front Med. 2023 Feb.

Abstract

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.

Keywords: driver mutations; immune-checkpoint inhibitors; non-small cell lung cancer; resistant mechanism; treatment strategy.

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