Zhiying Wang,1,* Zhixian Zhong,2,* Wenxiao Yang,1 Yun Li,3 Ke Zhang,3 Yabin Gong,1 Lijing Jiao,1,4 Ling Xu1,4 

1Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China; 2Department of Oncology, East Hospital Affiliated to Tongji University, School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of China; 3Department of Oncology, Shanghai Integrated Traditional Chinese and Western Medicine Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200082, People’s Republic of China; 4Institute of Translational Cancer Research for Integrated Chinese and Western Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Ling Xu, Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Shanghai, 200437, People’s Republic of China, Email doctor200004@163.com Lijing Jiao, Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Shanghai, 200437, People’s Republic of China, Email jlj969@163.com

Abstract: Nonsmall cell lung cancer (NSCLC) accounts for 85% of all cases of lung cancer cases. Epidermal growth factor receptor (EGFR) with L858R/T790M mutations are commonly found in clinical practice and usually results in resistance to first- and second-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Osimertinib is currently the first-line treatment choice for patients with EGFR L858R/T790M mutations, however, as to other EGFR-TKIs, resistance inevitably occurs. There is substantial evidence supporting the efficacy of traditional Chinese medicine (TCM) in the prevention and treatment of non-small cell lung cancer (NSCLC). The mechanisms underlying these effects involve the modulation of key cellular processes, including proliferation, apoptosis, cell cycle regulation, migration, invasion, autophagy, and epithelial–mesenchymal transition. TCM achieves these effects by regulating multiple signaling pathways and mechanisms, while also exhibiting synergistic interactions with EGFR tyrosine kinase inhibitors (TKIs). This review highlights the mechanisms through which TCM influences NSCLC patients harboring EGFR mutations, offering a promising therapeutic strategy for those with EGFR-TKI resistance.

Keywords: traditional Chinese medicine, NSCLC, EGFR, L858R/T790M mutations