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

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

non-small cell lung cancer / driver mutations / treatment strategy / resistant mechanism / immune-checkpoint inhibitors

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Acknowledgements

This work was supported by 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).

Compliance with ethics guidelines

Jia Zhong, Hua Bai, Zhijie Wang, Jianchun Duan, Wei Zhuang, Di Wang, Rui Wan, Jiachen Xu, Kailun Fei, Zixiao Ma, Xue Zhang, and Jie Wang declare no potential conflicts of interest. This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

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