There is currently a dearth of information regarding lung cancer in never smokers (LCINS). Additionally, there is a difference in somatic mutations, tumour mutational burden, and chromosomal aberrations between smokers and never smokers (NS), insinuating a different disease entity in LCINS. A better understanding of actionable driver alterations prevalent in LCINS and the genomic landscape will contribute to identifying new molecular targets of relevance for NS that will drastically improve outcomes. Differences in treatment outcomes between NS and smokers, as well as sexes, with NSCLC suggest unique tumour characteristics. Epidermal growth factor receptor (EGFR) tyrosine kinase mutations and echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) gene rearrangements are more common in NS and have been associated with chemotherapy resistance. Moreover, NS are less likely to benefit from immune mediators including PD-L1. Unravelling the genomic and epigenomic underpinnings of LCINS will aid in the development of not only novel targeted therapies but also more refined approaches. This review encompasses driver genes and pathways involved in the pathogenesis of LCINS and a deeper exploration of the genomic landscape and tumour microenvironment. We highlight the dire need to define the genetic and environmental aspects entailing the development of lung cancer in NS.
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Huazhong Univ Sci & Technol, Ctr Canc, Union Hosp, Tongji Med Coll, Wuhan 430074, Hubei, Peoples R ChinaHuazhong Univ Sci & Technol, Ctr Canc, Union Hosp, Tongji Med Coll, Wuhan 430074, Hubei, Peoples R China
Ren, Jing-Hua
He, Wen-Shan
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Huazhong Univ Sci & Technol, Dept Gen Surg, Union Hosp, Tongji Med Coll, Wuhan 430074, Hubei, Peoples R ChinaHuazhong Univ Sci & Technol, Ctr Canc, Union Hosp, Tongji Med Coll, Wuhan 430074, Hubei, Peoples R China
He, Wen-Shan
Yan, Guo-Li
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Huazhong Univ Sci & Technol, Ctr Canc, Union Hosp, Tongji Med Coll, Wuhan 430074, Hubei, Peoples R ChinaHuazhong Univ Sci & Technol, Ctr Canc, Union Hosp, Tongji Med Coll, Wuhan 430074, Hubei, Peoples R China
Yan, Guo-Li
Jin, Min
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Huazhong Univ Sci & Technol, Ctr Canc, Union Hosp, Tongji Med Coll, Wuhan 430074, Hubei, Peoples R ChinaHuazhong Univ Sci & Technol, Ctr Canc, Union Hosp, Tongji Med Coll, Wuhan 430074, Hubei, Peoples R China
Jin, Min
Yang, Kun-Yu
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Huazhong Univ Sci & Technol, Ctr Canc, Union Hosp, Tongji Med Coll, Wuhan 430074, Hubei, Peoples R ChinaHuazhong Univ Sci & Technol, Ctr Canc, Union Hosp, Tongji Med Coll, Wuhan 430074, Hubei, Peoples R China
Yang, Kun-Yu
Wu, Gang
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Huazhong Univ Sci & Technol, Ctr Canc, Union Hosp, Tongji Med Coll, Wuhan 430074, Hubei, Peoples R ChinaHuazhong Univ Sci & Technol, Ctr Canc, Union Hosp, Tongji Med Coll, Wuhan 430074, Hubei, Peoples R China
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Chonnam Natl Univ, Dept Internal Med, Med Sch, Gwangju, South KoreaChonnam Natl Univ, Dept Internal Med, Med Sch, Gwangju, South Korea
Park, Ha-Young
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Oh, Hyung-Joo
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Park, Hwa Kyung
Yoon, Joon-Young
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Chonnam Natl Univ, Dept Internal Med, Med Sch, Gwangju, South Korea
Chonnam Natl Univ, Lung Canc Ctr, Hwasun Hosp, Hwasun, South KoreaChonnam Natl Univ, Dept Internal Med, Med Sch, Gwangju, South Korea
Yoon, Joon-Young
Yoon, Chang-Seok
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Chonnam Natl Univ, Dept Internal Med, Med Sch, Gwangju, South KoreaChonnam Natl Univ, Dept Internal Med, Med Sch, Gwangju, South Korea
Yoon, Chang-Seok
Kho, Bo Gun
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Chonnam Natl Univ, Dept Internal Med, Med Sch, Gwangju, South KoreaChonnam Natl Univ, Dept Internal Med, Med Sch, Gwangju, South Korea
Kho, Bo Gun
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Kim, Tae-Ok
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Shin, Hong-Joon
Park, Chul-Kyu
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Chonnam Natl Univ, Dept Internal Med, Med Sch, Gwangju, South Korea
Chonnam Natl Univ, Lung Canc Ctr, Hwasun Hosp, Hwasun, South KoreaChonnam Natl Univ, Dept Internal Med, Med Sch, Gwangju, South Korea
Park, Chul-Kyu
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Kwon, Yong-Soo
Kim, Yu-Il
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Chonnam Natl Univ, Dept Internal Med, Med Sch, Gwangju, South KoreaChonnam Natl Univ, Dept Internal Med, Med Sch, Gwangju, South Korea
Kim, Yu-Il
Lim, Sung-Chul
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Chonnam Natl Univ, Dept Internal Med, Med Sch, Gwangju, South KoreaChonnam Natl Univ, Dept Internal Med, Med Sch, Gwangju, South Korea