Oncogenic mutations in non-small cell lung cancer: from molecular mechanisms to clinical practice.
4 affiliations
- 1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
- 2Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
- 3Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China. [email protected].
- 4Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China. [email protected].
Abstract
Targeted therapy has revolutionized the treatment of non-small cell lung cancer (NSCLC) patients harboring oncogenic alterations, and next-generation tyrosine kinase inhibitors (TKIs) significantly increase blood-brain barrier (BBB) penetration, leading to improved disease control and survival benefits. However, several issues remain to be addressed, including the selection of more appropriate and individualized agents, the emergence of TKI resistance, and the challenging management of central nervous system (CNS) progression. In this review, we comprehensively summarize the efficacy and safety of TKIs and targeted specific antibodies in advanced or metastatic patients with common or rare mutations, providing guidance in selecting the optimal agent. We further explore the mechanisms underlying drug resistance and regimens aimed at overcoming resistance. In nonmetastatic resectable or unresectable NSCLC, we discuss the therapeutic potential of targeted agents and current issues requiring further research. In addition, we distinguish current and potential therapeutic strategies for patients with baseline brain metastasis (BM) and those without baseline BM who subsequently develop brain progression, leading to more effective and personalized treatment. Finally, we provide perspectives on challenges and future directions in the identification and treatment of oncogenic alterations, particularly in the context of co-mutations and the heterogeneous nature of metastases, and emphasize the clinical importance of artificial intelligence (AI)-assisted genetic testing and biomarker development.
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BibTeX
@article{li2026oncogenic,
title = {{Oncogenic mutations in non-small cell lung cancer: from molecular mechanisms to clinical practice.}},
author = {Chaozhuo Li and Xiaoyan Yin and Shujie Zhou and Junxu Wen and Jinming Yu and Xiangjiao Meng},
journal = {Signal transduction and targeted therapy},
year = {2026},
month = oct,
doi = {10.1038/s41392-026-02689-2},
url = {https://europepmc.org/article/MED/42894004},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Oncogenic mutations in non-small cell lung cancer: from molecular mechanisms to clinical practice.
AU - Chaozhuo Li
AU - Xiaoyan Yin
AU - Shujie Zhou
AU - Junxu Wen
AU - Jinming Yu
AU - Xiangjiao Meng
PY - 2026
DA - 2026/10/19
JO - Signal transduction and targeted therapy
DO - 10.1038/s41392-026-02689-2
UR - https://europepmc.org/article/MED/42894004
AB - Targeted therapy has revolutionized the treatment of non-small cell lung cancer (NSCLC) patients harboring oncogenic alterations, and next-generation tyrosine kinase inhibitors (TKIs) significantly increase blood-brain barrier (BBB) penetration, leading to improved disease control and survival benefits. However, several issues remain to be addressed, including the selection of more appropriate and individualized agents, the emergence of TKI resistance, and the challenging management of central nervous system (CNS) progression. In this review, we comprehensively summarize the efficacy and safety of TKIs and targeted specific antibodies in advanced or metastatic patients with common or rare mutations, providing guidance in selecting the optimal agent. We further explore the mechanisms underlying drug resistance and regimens aimed at overcoming resistance. In nonmetastatic resectable or unresectable NSCLC, we discuss the therapeutic potential of targeted agents and current issues requiring further research. In addition, we distinguish current and potential therapeutic strategies for patients with baseline brain metastasis (BM) and those without baseline BM who subsequently develop brain progression, leading to more effective and personalized treatment. Finally, we provide perspectives on challenges and future directions in the identification and treatment of oncogenic alterations, particularly in the context of co-mutations and the heterogeneous nature of metastases, and emphasize the clinical importance of artificial intelligence (AI)-assisted genetic testing and biomarker development.
SN - 2095-9907
SN - 2059-3635
ER -