肺癌是美国及世界上在男性和女性中的与癌症有关的第一位的死亡原因。
据4月7日的《科学 - 转化医学》杂志报道说，在当前或从前的吸烟者的肺中存在着一个具有指示性的生物化学通路，该通路可帮助人们找到那些具有最高风险的发生肺癌的人。
引人注目的是，这一通路可在癌症开始发生之前被逆转，它预示着在高风险吸烟者中的第一个可能有效地预防肺癌的方法。 这是一个在肺癌早期发现领域的关键性的敲门砖，因为目前还没有方法来辨识出那些在吸烟者中的占10-20%的会生肺癌的人，而美国的当前和以前的吸烟者有9000万人之多。 总的来说，这些发现可能帮助解决巨大的且在不断增长的公共卫生方面的与肺癌有关的负担问题。
在此项研究中，Adam Gustafson及其同僚在具有或没有肺癌的吸烟者中以及那些具有较高罹患肺癌风险的人中检测了在覆衬着主要肺气道的细胞中的属于不同的与癌症有关的通路的基因表达水平。 他们发现，与没有生肺癌的吸烟者相比，属于某一种特别的与癌症有关的通路（即PI3K通路）的基因会在那些气道中有肺癌或癌性病灶的吸烟者中被激活至更高的水平。 更值得注意的是，研究人员发现，在接受了某种可能的肺癌药物（叫做肌醇，myo-inositol）的治疗之后，PI3K通路的活性会在高风险吸烟者的气道中下降，其癌性病变会消退；肌醇是通过阻断PI3K通路而发生功效的。 将来，这种检测方法还可扩大至其它的也会接触香烟的那些细胞之中，如覆衬于鼻腔和口腔的细胞；这种方法可能会成为大面积筛检肺癌的一种工具。(生物谷Bioon.com)
更多阅读
Nature：吸烟导致基因突变致癌
PNAS：一种分子可能造成不吸烟者患肺癌
The Lancet Oncology：非烟民患肺癌关键基因GPC5
Nature：肺癌和皮肤癌完整基因图谱测序成功
生物谷推荐原文出处：
Sci Transl Med DOI: 10.1126/scitranslmed.3000251
Airway PI3K Pathway Activation Is an Early and Reversible Event in Lung Cancer Development
Adam M. Gustafson1,2,*, Raffaella Soldi3,*, Christina Anderlind1, Mary Beth Scholand4, Jun Qian5, Xiaohui Zhang1, Kendal Cooper3, Darren Walker3, Annette McWilliams6, Gang Liu1, Eva Szabo7, Jerome Brody1, Pierre P. Massion5, Marc E. Lenburg1,2,8, Stephen Lam6, Andrea H. Bild3,*? and Avrum Spira1,2,8,*?
Although only a subset of smokers develop lung cancer, we cannot determine which smokers are at highest risk for cancer development, nor do we know the signaling pathways altered early in the process of tumorigenesis in these individuals. On the basis of the concept that cigarette smoke creates a molecular field of injury throughout the respiratory tract, this study explores oncogenic pathway deregulation in cytologically normal proximal airway epithelial cells of smokers at risk for lung cancer. We observed a significant increase in a genomic signature of phosphatidylinositol 3-kinase (PI3K) pathway activation in the cytologically normal bronchial airway of smokers with lung cancer and smokers with dysplastic lesions, suggesting that PI3K is activated in the proximal airway before tumorigenesis. Further, PI3K activity is decreased in the airway of high-risk smokers who had significant regression of dysplasia after treatment with the chemopreventive agent myo-inositol, and myo-inositol inhibits the PI3K pathway in vitro. These results suggest that deregulation of the PI3K pathway in the bronchial airway epithelium of smokers is an early, measurable, and reversible event in the development of lung cancer and that genomic profiling of these relatively accessible airway cells may enable personalized approaches to chemoprevention and therapy. Our work further suggests that additional lung cancer chemoprevention trials either targeting the PI3K pathway or measuring airway PI3K activation as an intermediate endpoint are warranted.
