Molecular Profiles for Lung Cancer Pathogenesis and Detection in U.S. Veterans
Final rept. 20 Sep 2010-19 Sep 2014
CALIFORNIA UNIV LOS ANGELES
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Uncertainty about the clinical behavior of a premalignant lesion can lead to either inappropriate inaction or inappropriate aggressive treatment, either of which can result in harm to the patient. The main goal of this DOD research program was to shed light on the molecular mechanisms of airway field cancerization and development of premalignant lesions. During this grant, we investigated and began to understand complex mechanisms that lead to field of cancerization, including genomic aberrations and microRNA and gene expression changes. We have characterized the transcriptomic architecture of the airway field cancerization in early-stage NSCLC and validated the expression of novel field cancerization markers in airways and tumors. Furthermore, we understood how the molecular field of injury evolves spatiotemporally and identified gradient profiles in the field cancerization that highly embody the nearby lung tumors. We identified field of cancerization biomarkers that are specific to NSCLC vs benign pulmonary nodules and can detect lung cancer when assessed in minimally invasive sites in the airways. We anticipate that our results will allow for the development of chemopreventive andor therapeutic strategies that are effective during the window of opportunity when lung cancer is still subclinical. Future translation of these results could lead to a paradigm shift in the way in which we address the clinical problem of the individual at high risk for lung cancer.
- Medicine and Medical Research