Lung cancer is the most common cause of cancer-related deaths globally. Although smoking-related lung cancers continue to account for the majority of diagnoses, smoking rates have been decreasing for several decades. Lung cancer in individuals who have never smoked (LCINS) is estimated to be the fifth most common cause of cancer-related deaths worldwide in 2023, preferentially occurring in women and Asian populations. As smoking rates continue to decline, understanding the aetiology and features of this disease, which necessitate unique diagnostic and treatment paradigms, will be imperative. New data have provided important insights into the molecular and genomic characteristics of LCINS, which are distinct from those of smoking-associated lung cancers and directly affect treatment decisions and outcomes. Herein, we review the emerging data regarding the aetiology and features of LCINS, particularly the genetic and environmental underpinnings of this disease as well as their implications for treatment. In addition, we outline the unique diagnostic and therapeutic paradigms of LCINS and discuss future directions in identifying individuals at high risk of this disease for potential screening efforts.

肺癌是全球癌症相关死亡的最常见原因。尽管与吸烟相关的肺癌仍然占诊断的大多数，但吸烟率几十年来一直在下降。据估计，到 2023 年，从不吸烟者的肺癌 (LCINS) 将成为全球第五大癌症相关死亡原因，主要发生在女性和亚洲人群中。随着吸烟率持续下降，了解这种疾病的病因和特征势在必行，这需要独特的诊断和治疗范例。新数据为了解 LCINS 的分子和基因组特征提供了重要见解，这些特征与吸烟相关的肺癌不同，直接影响治疗决策和结果。在此，我们回顾了有关 LCINS 病因学和特征的新数据，特别是该疾病的遗传和环境基础及其对治疗的影响。此外，我们概述了 LCINS 独特的诊断和治疗范例，并讨论了识别该疾病高风险个体以进行潜在筛查工作的未来方向。