肺癌是美國及世界上在男性和女性中的與癌癥有關(guān)的第一位的死亡原因,。
據(jù)4月7日的《科學(xué) - 轉(zhuǎn)化醫(yī)學(xué)》雜志報(bào)道說，在當(dāng)前或從前的吸煙者的肺中存在著一個(gè)具有指示性的生物化學(xué)通路,，該通路可幫助人們找到那些具有最高風(fēng)險(xiǎn)的發(fā)生肺癌的人,。
引人注目的是，這一通路可在癌癥開始發(fā)生之前被逆轉(zhuǎn),，它預(yù)示著在高風(fēng)險(xiǎn)吸煙者中的第一個(gè)可能有效地預(yù)防肺癌的方法,。 這是一個(gè)在肺癌早期發(fā)現(xiàn)領(lǐng)域的關(guān)鍵性的敲門磚，因?yàn)槟壳斑€沒有方法來辨識出那些在吸煙者中的占10-20%的會生肺癌的人,，而美國的當(dāng)前和以前的吸煙者有9000萬人之多,。 總的來說，這些發(fā)現(xiàn)可能幫助解決巨大的且在不斷增長的公共衛(wèi)生方面的與肺癌有關(guān)的負(fù)擔(dān)問題,。
在此項(xiàng)研究中,，Adam Gustafson及其同僚在具有或沒有肺癌的吸煙者中以及那些具有較高罹患肺癌風(fēng)險(xiǎn)的人中檢測了在覆襯著主要肺氣道的細(xì)胞中的屬于不同的與癌癥有關(guān)的通路的基因表達(dá)水平。 他們發(fā)現(xiàn),，與沒有生肺癌的吸煙者相比,，屬于某一種特別的與癌癥有關(guān)的通路（即PI3K通路）的基因會在那些氣道中有肺癌或癌性病灶的吸煙者中被激活至更高的水平。 更值得注意的是,，研究人員發(fā)現(xiàn),，在接受了某種可能的肺癌藥物（叫做肌醇，myo-inositol）的治療之后,，PI3K通路的活性會在高風(fēng)險(xiǎn)吸煙者的氣道中下降,，其癌性病變會消退；肌醇是通過阻斷PI3K通路而發(fā)生功效的,。 將來,，這種檢測方法還可擴(kuò)大至其它的也會接觸香煙的那些細(xì)胞之中，如覆襯于鼻腔和口腔的細(xì)胞,；這種方法可能會成為大面積篩檢肺癌的一種工具,。(生物谷Bioon.com)
更多閱讀
Nature：吸煙導(dǎo)致基因突變致癌
PNAS：一種分子可能造成不吸煙者患肺癌
The Lancet Oncology：非煙民患肺癌關(guān)鍵基因GPC5
Nature：肺癌和皮膚癌完整基因圖譜測序成功
生物谷推薦原文出處：
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.
