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.
机构:
Kyoto Univ Hosp, Dept Clin Trial Design & Management, Translat Res Ctr, Sakyo Ku, Kyoto 6068507, JapanKyoto Univ Hosp, Dept Clin Trial Design & Management, Translat Res Ctr, Sakyo Ku, Kyoto 6068507, Japan
Tanaka, Shiro
Yanagihara, Kazuhiro
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Kyoto Univ Hosp, Outpatient Oncol Unit, Sakyo Ku, Kyoto 6068507, Japan
Kyoto Univ, Grad Sch Med, Dept Translat Clin Oncol, Sakyo Ku, Kyoto 6068507, JapanKyoto Univ Hosp, Dept Clin Trial Design & Management, Translat Res Ctr, Sakyo Ku, Kyoto 6068507, Japan
Yanagihara, Kazuhiro
Tamaru, Satoshi
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Mie Univ, Fac Med, Inst Human Res Promot & Drug Dev, Tsu, Mie 5148507, Japan
Kyoto Univ Hosp, Dept Clin Innovat Med, Translat Res Ctr, Sakyo Ku, Kyoto 6068507, JapanKyoto Univ Hosp, Dept Clin Trial Design & Management, Translat Res Ctr, Sakyo Ku, Kyoto 6068507, Japan
Tamaru, Satoshi
Teramukai, Satoshi
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Kyoto Univ Hosp, Dept Clin Trial Design & Management, Translat Res Ctr, Sakyo Ku, Kyoto 6068507, JapanKyoto Univ Hosp, Dept Clin Trial Design & Management, Translat Res Ctr, Sakyo Ku, Kyoto 6068507, Japan
Teramukai, Satoshi
Kitano, Toshiyuki
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Kyoto Univ Hosp, Outpatient Oncol Unit, Sakyo Ku, Kyoto 6068507, Japan
Kyoto Univ, Grad Sch Med, Dept Translat Clin Oncol, Sakyo Ku, Kyoto 6068507, JapanKyoto Univ Hosp, Dept Clin Trial Design & Management, Translat Res Ctr, Sakyo Ku, Kyoto 6068507, Japan
Kitano, Toshiyuki
Fukushima, Masanori
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Kyoto Univ Hosp, Dept Clin Trial Design & Management, Translat Res Ctr, Sakyo Ku, Kyoto 6068507, Japan
Kyoto Univ Hosp, Outpatient Oncol Unit, Sakyo Ku, Kyoto 6068507, Japan
Translat Res Informat Ctr, Chuo Ku, Kobe, Hyogo 6500047, JapanKyoto Univ Hosp, Dept Clin Trial Design & Management, Translat Res Ctr, Sakyo Ku, Kyoto 6068507, Japan
机构:
Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol,Dept Med, Boston, MA 02215 USAHarvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol,Dept Med, Boston, MA 02215 USA
Gaughan, Elizabeth M.
Cryer, Sarah K.
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Harvard Univ, Sch Med, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol,Dept Med Oncol, Boston, MA 02115 USAHarvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol,Dept Med, Boston, MA 02215 USA
Cryer, Sarah K.
Yeap, Beow Y.
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Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USAHarvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol,Dept Med, Boston, MA 02215 USA
Yeap, Beow Y.
Jackman, David M.
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Harvard Univ, Sch Med, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol,Dept Med Oncol, Boston, MA 02115 USAHarvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol,Dept Med, Boston, MA 02215 USA
Jackman, David M.
Costa, Daniel B.
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Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol,Dept Med, Boston, MA 02215 USAHarvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol,Dept Med, Boston, MA 02215 USA
机构:
Univ Santiago de Compostela, Dept Prevent Med & Publ Hlth, Santiago De Compostela, Spain
CIBERESP, Barcelona, Spain
Brown Univ, Dept Epidemiol, Brown Sch Publ Hlth, Providence, RI 02912 USAUniv Hosp Complex Vigo, Serv Pneumol, Vigo, Spain
Ruano-Ravina, Alberto
Kelsey, Karl T.
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Brown Univ, Dept Epidemiol, Brown Sch Publ Hlth, Providence, RI 02912 USAUniv Hosp Complex Vigo, Serv Pneumol, Vigo, Spain
机构:
Univ Santiago de Compostela, Dept Prevent Med & Publ Hlth, Santiago De Compostela, Spain
CIBERESP, Barcelona, Spain
Univ Hosp Complex Santiago de Compostela, Serv Prevent Med, Santiago De Compostela, SpainUniv Hosp Complex Vigo, Serv Pneumol, Vigo, Spain
机构:
Washington Univ, Sch Med, Dept Internal Med, Div Oncol, St Louis, MO 63110 USA
Washington Univ, Sch Med, Genome Inst, St Louis, MO 63110 USA
Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USAWashington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA
Ding, Li
Griffith, Malachi
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Washington Univ, Sch Med, Genome Inst, St Louis, MO 63110 USA
Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USAWashington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA
Griffith, Malachi
Subramanian, Janakiraman
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Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA
Washington Univ, Sch Med, Dept Internal Med, Div Oncol, St Louis, MO 63110 USAWashington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA
Subramanian, Janakiraman
Dees, Nathan D.
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Washington Univ, Sch Med, Genome Inst, St Louis, MO 63110 USAWashington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA
Dees, Nathan D.
Kanchi, Krishna L.
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Washington Univ, Sch Med, Genome Inst, St Louis, MO 63110 USAWashington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA
Kanchi, Krishna L.
Maher, Christopher A.
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Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA
Washington Univ, Sch Med, Dept Internal Med, Div Oncol, St Louis, MO 63110 USA
Washington Univ, Sch Med, Genome Inst, St Louis, MO 63110 USAWashington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA
Maher, Christopher A.
Fulton, Robert
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Washington Univ, Sch Med, Genome Inst, St Louis, MO 63110 USA
Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USAWashington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA
Fulton, Robert
Fulton, Lucinda
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Washington Univ, Sch Med, Genome Inst, St Louis, MO 63110 USA
Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USAWashington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA
Fulton, Lucinda
Wallis, John
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Washington Univ, Sch Med, Genome Inst, St Louis, MO 63110 USA
Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USAWashington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA
Wallis, John
Chen, Ken
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机构:
Univ Texas MD Anderson Canc Ctr, Div Quantitat Sci, Dept Bioinformat & Computat Biol, Houston, TX 77030 USAWashington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA
Chen, Ken
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Walker, Jason
McDonald, Sandra
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Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA
Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USAWashington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA
McDonald, Sandra
Bose, Ron
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Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA
Washington Univ, Sch Med, Dept Internal Med, Div Oncol, St Louis, MO 63110 USAWashington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA
Bose, Ron
Ornitz, David
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Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USAWashington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA
Ornitz, David
Xiong, Donghai
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机构:
Med Coll Wisconsin, Dept Pharmacol & Toxicol, Milwaukee, WI 53226 USAWashington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA
Xiong, Donghai
You, Ming
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Med Coll Wisconsin, Dept Pharmacol & Toxicol, Milwaukee, WI 53226 USAWashington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA
You, Ming
Dooling, David J.
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Washington Univ, Sch Med, Genome Inst, St Louis, MO 63110 USA
Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USAWashington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA
Dooling, David J.
Watson, Mark
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Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA
Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USAWashington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA
Watson, Mark
Mardis, Elaine R.
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机构:
Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA
Washington Univ, Sch Med, Genome Inst, St Louis, MO 63110 USA
Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USAWashington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA
Mardis, Elaine R.
Wilson, Richard K.
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Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA
Washington Univ, Sch Med, Genome Inst, St Louis, MO 63110 USA
Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USAWashington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA