Although only a subset of smokers develop lung cancer, we cannot determine which smokers are at highest\u00a0risk for cancer development, nor do we know the signaling pathways altered early in the process of tumorigenesis\u00a0in these individuals. On the basis of the concept that cigarette smoke creates a molecular field of injury\u00a0throughout the respiratory tract, this study explores oncogenic pathway deregulation in cytologically normal\u00a0proximal airway epithelial cells of smokers at risk for lung cancer. We observed a significant increase in a genomic\u00a0signature of phosphatidylinositol 3-kinase (PI3K) pathway activation in the cytologically normal bronchial airway of\u00a0smokers with lung cancer and smokers with dysplastic lesions, suggesting that PI3K is activated in the proximal\u00a0airway before tumorigenesis. Further, PI3K activity is decreased in the airway of high-risk smokers who had significant\u00a0regression of dysplasia after treatment with the chemopreventive agent myo-inositol, and myo-inositol inhibits\u00a0the PI3K pathway in vitro. These results suggest that deregulation of the PI3K pathway in the bronchial\u00a0airway epithelium of smokers is an early, measurable, and reversible event in the development of lung cancer\u00a0and that genomic profiling of these relatively accessible airway cells may enable personalized approaches to chemoprevention\u00a0and therapy. Our work further suggests that additional lung cancer chemoprevention trials either\u00a0targeting the PI3K pathway or measuring airway PI3K activation as an intermediate endpoint are warranted.<\/p>\n
For the journal article please click here<\/a>. <\/em><\/p>\n Media press releases:\u00a0 NBC Nightly News<\/a>,\u00a0Today Show<\/a>,\u00a0CBS<\/a> and BU News<\/a><\/em><\/p>\n","protected":false},"excerpt":{"rendered":" Although only a subset of smokers develop lung cancer, we cannot determine which smokers are at highest\u00a0risk for cancer development, nor do we know the signaling pathways altered early in the process of tumorigenesis\u00a0in these individuals. On the basis of the concept that cigarette smoke creates a molecular field of injury\u00a0throughout the respiratory tract, this […]<\/p>\n","protected":false},"author":4954,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[3],"tags":[],"_links":{"self":[{"href":"https:\/\/www.bumc.bu.edu\/compbiomed\/wp-json\/wp\/v2\/posts\/334"}],"collection":[{"href":"https:\/\/www.bumc.bu.edu\/compbiomed\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bumc.bu.edu\/compbiomed\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/compbiomed\/wp-json\/wp\/v2\/users\/4954"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/compbiomed\/wp-json\/wp\/v2\/comments?post=334"}],"version-history":[{"count":6,"href":"https:\/\/www.bumc.bu.edu\/compbiomed\/wp-json\/wp\/v2\/posts\/334\/revisions"}],"predecessor-version":[{"id":653,"href":"https:\/\/www.bumc.bu.edu\/compbiomed\/wp-json\/wp\/v2\/posts\/334\/revisions\/653"}],"wp:attachment":[{"href":"https:\/\/www.bumc.bu.edu\/compbiomed\/wp-json\/wp\/v2\/media?parent=334"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/compbiomed\/wp-json\/wp\/v2\/categories?post=334"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/compbiomed\/wp-json\/wp\/v2\/tags?post=334"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}