Lung cancer is a leading cause of cancer-related mortality across the world. Although the majority of lung cancer is attributed to tobacco smoke, approximately 25% of lung cancers worldwide occur in lifelong never smokers. Over the past decades, the bulk of research on this disease suggested that several genetic, environmental, hormonal, and viral factors might increase the risk of lung cancer among never smokers. However, there has been no dominant risk factor whose significance has been validated across racial and ethnic groups. However, this subset of lung cancers has received renewed attention due to the introduction of the epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitors showing the dramatic therapeutic response on selected patients with activating EGFR mutations which occur more commonly in never smokers. The treatment strategy blocking EGFR pathway in EGFR-mutant lung cancer represents a remarkable example of molecular targeted therapies which completely repress tumor by inhibition of driving oncogenes. More recently, a surprising positive effect of an ALK inhibitor on EML4-ALK-positive lung cancer has been suggested that lung cancer in never smokers is likely to be an assemblage of molecularly defined subsets which would be a good candidate for personalized diagnostic and therapeutic approaches.
Bibliographical noteFunding Information:
Dr. Cho reports receiving lecture fees from Roche and Astrazeneca, and consulting fees from Bristol-Myers Squibb and GlaxoSmithKline; Dr. Mitsudomi receiving honoraria from AstraZeneca, Chugai, Daiichi-Sankyo, Pfizer, and Taiho and attending the advisory board meeting of Pfizer, Boeringer-Ingelheim, AstraZeneca, Kyowa-Kirin, Bayer, and Chugai; and Dr. Mok receiving consulting fees from Roche, Astra-Zeneca, Pfizer, and Eli Lilly, lecture fees from Roche, AstraZeneca, and Eli Lilly, and a research grant to the Chinese Lung Cancer Research Foundation from AstraZeneca, Hong Kong. No other potential conflict of interest relevant to this article was reported.
This study was supported in part by a faculty research grant of Yonsei University College of Medicine for 6-2010-0061 , and by a grant of the Korean Health Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea ( A101956 ).
All Science Journal Classification (ASJC) codes
- Pulmonary and Respiratory Medicine
- Cancer Research