Submitted:
22 October 2026
Posted:
22 October 2026
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Abstract
Lung cancer is one of the leading causes of cancer-related mortality worldwide, and neoadjuvant therapy has become a cornerstone in the management of resectable non-small cell lung cancer (NSCLC). Growing evidence suggests that smoking history is an important clinical and biological factor that influences response to neoadjuvant treatment. This review synthesizes epidemiologic, translational, and clinical evidence, including findings from landmark clinical trials. It aims to evaluate the efficacy of neo-adjuvant chemotherapy, immunotherapy, targeted therapy, and multimodal treatment strategies according to smoking status. Furthermore, this review examines the molecular and immunologic mechanisms underlying the differential treatment responses observed among current, former, and never-smokers. Ultimately, there is an increasing need to conduct prospective smoking-stratified studies and integrate smoking history into medical practice to develop more personalized neoadjuvant therapies for patients with lung cancer.
Keywords:
never-smoker
; non-small cell lung cancer
; lung cancer
; neoadjuvant therapy
; perioperative therapy
; United States
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