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Lung cancers unrelated to smoking: characterized by single oncogene addiction?

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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.

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Acknowledgments

This study is supported in part by a Grant-in-Aid for Scientific Research (B) from the Japan Society for the Promotion of Science (20903076) and a grant from the Kobayashi Institute for Innovative Cancer Chemotherapy.

Conflict of interest

T. Mitsudomi serves as a consultant to Pfizer and Boehringer Ingelheim, and received honoraria from AstraZeneca and Chugai Pharmaceutical.

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Authors and Affiliations

  1. Department of Thoracic Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan

    Kenichi Suda, Kenji Tomizawa & Tetsuya Mitsudomi

  2. Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan

    Yasushi Yatabe

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  1. Kenichi Suda
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Correspondence to Tetsuya Mitsudomi.

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Suda, K., Tomizawa, K., Yatabe, Y. et al. Lung cancers unrelated to smoking: characterized by single oncogene addiction?. Int J Clin Oncol 16, 294–305 (2011). https://doi.org/10.1007/s10147-011-0262-y

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