Grant Recipient: Dr.
Title of Project: Biomarkers of pre-malignant disease progression for lung cancer detection
Sponsoring Institution: Boston University, B U Medical Campus
Lung cancer is the leading cause of cancer death. Recently, the National Lung Cancer Screening Trial reported a 20% reduction in lung cancer mortality and three lung cancer chemoprevention trials report reductions in markers associated with lung cancer development. These studies highlight the possibilities for further reductions in lung cancer mortality through early detection and chemoprevention strategies among high-risk smokers. Our group has previously identified smoking- and lung cancer-specific molecular alterations in the epithelial cells that line the major airways which can be obtained during bronchoscopy. In this study, we propose to use next generation sequencing technology to quantify RNA expression alterations (RNA-Seq) in normal airway epithelial cells in patients with and without precancerous lesions in their airways. We will characterize how RNA expression is affected by the presence of precancerous lesions and identify RNA expression changes that predict if the lesions will progress or regress. The predictors will be important in selecting which high-risk smokers to enroll in chemoprevention trials, identifying which smokers are benefiting from the therapy, and identifying new targets for chemoprevention. Finally, we will test whether our RNA expression predictors are associated with the presence or future development of lung cancer. Common biology between RNA expression alterations in normal airway epithelial cells of patients with precancerous lesions and patients with lung cancer may indicate early events in lung carcinogenesis and have additional utility as early markers of lung cancer.