title: Lung cancers unrelated to smoking: characterized by single oncogene addiction?
abstract: Lung cancer is a major cause of cancer-related mortality worldwide. Currently, adenocarcinoma is its most common histological subtype in many countries. In contrast with small cell lung cancer or squamous cell carcinoma, lung adenocarcinoma often arises in never-smokers, especially in East Asian countries, as well as in smokers. Adenocarcinoma in never-smokers is associated with a lower incidence of genetic alterations (i.e., somatic mutations, loss of heterozygosity, and methylation) than in smokers. In addition, most adenocarcinomas in never-smokers harbor one of the proto-oncogene aberrations that occur in a mutually exclusive manner (EGFR mutation, KRAS mutation, HER2 mutations, or ALK translocation). It is of note that the proliferation and survival of lung cancer cells that harbor one of these oncogenic aberrations depend on the signaling from each aberrantly activated oncoprotein (oncogene addiction). Therefore, most adenocarcinomas in never-smokers can be effectively treated by molecularly targeted drugs that inhibit each oncoprotein. Moreover, from a pathological aspect, lung adenocarcinoma in never-smokers is characterized by terminal respiratory unit-type adenocarcinoma and a particular gene expression profile. Finally, epidemiological analyses have identified many candidate causes of lung cancer in never-smokers (genetic, environmental, and hormonal factors). The elucidation of the particular features of lung cancer unrelated to smoking and the development of new therapeutic modalities may reduce the mortality from lung cancers in the future.
authors.affiliation: Department of Thoracic Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Suda
authors.forename: Kenji
authors.initials: K
authors.lastname: Tomizawa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yatabe
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mitsudomi
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000453:epidemiology* / Q000473:pathology; D002869:Chromosome Aberrations; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D008297:Male; D058990:Molecular Targeted Therapy; D009154:Mutation; D009367:Neoplasm Staging; D016273:Occupational Exposure; D015513:Oncogene Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012907:Smoking / Q000453:epidemiology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
chemical_list: C522504:EML4-ALK fusion protein, human; C117307:KRAS protein, human; C000715470:MAS1 protein, human; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins