Lung Cancer in Never Smokers: Molecular Profiles and Therapeutic Implications

被引:116
作者
Rudin, Charles M. [1 ]
Avila-Tang, Erika
Harris, Curtis C. [2 ]
Herman, James G.
Hirsch, Fred R. [3 ]
Pao, William [4 ]
Schwartz, Ann G. [5 ]
Vahakangas, Kirsi H. [6 ]
Samet, Jonathan M.
机构
[1] Johns Hopkins Univ, Sch Med, Baltimore, MD 21231 USA
[2] NCI, Bethesda, MD 20892 USA
[3] Univ Colorado, Denver, CO 80202 USA
[4] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA
[5] Wayne State Univ, Detroit, MI USA
[6] Univ Kuopio, FIN-70211 Kuopio, Finland
关键词
GROWTH-FACTOR-RECEPTOR; ENVIRONMENTAL TOBACCO-SMOKE; PHASE-III TRIAL; PREVIOUSLY TREATED PATIENTS; COAL COMBUSTION EMISSIONS; P53 MUTATION HOTSPOT; REPAIR GENE XRCC1; S-TRANSFERASE M1; K-RAS GENES; DNA-REPAIR;
D O I
10.1158/1078-0432.CCR-09-0377
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The majority of lung cancers are caused by long term exposure to the several classes of carcinogens present in tobacco smoke. Although a significant fraction of lung cancers in never smokers may also be attributable to tobacco, many such cancers arise in the absence of detectable tobacco exposure, and may follow a very different cellular and molecular pathway of malignant transformation. Recent studies summarized here suggest that lung cancers arising in never smokers have a distinct natural history, profile of oncogenic mutations, and response to targeted therapy. The majority of molecular analyses of lung cancer have focused on genetic profiling of pathways responsible for metabolism of primary tobacco carcinogens. Limited research has been conducted evaluating familial aggregation and genetic linkage of lung cancer, particularly among never smokers in whom such associations might be expected to be strongest. Data emerging over the past several years show that lung cancers in never smokers are much more likely to carry activating mutations of the epidermal growth factor receptor (EGFR), a key oncogenic factor and direct therapeutic target of several newer anticancer drugs. EGFR mutant lung cancers may represent a distinct class of lung cancers, enriched in the never-smoking population, and less clearly linked to direct tobacco carcinogenesis. These insights followed initial testing and demonstration of efficacy of EGFR-targeted drugs. Focused analysis of molecular carcinogenesis in lung cancers in never smokers is needed, and may provide additional biologic insight with therapeutic implications for lung cancers in both ever smokers and never smokers. (Clin Cancer Res 2009;15(18):5646-61)
引用
收藏
页码:5646 / 5661
页数:16
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