NCE (Year 6)
During this reporting period we discovered and published on how reactive oxygen species drive proliferation of airway basal stem cells. We found that this pathway is critical for homeostasis of the airway epithelium and perturbing this pathway results in precancerous lesions. Interestingly, these precancerous lesions are able to resolve over time, which is similar to the situation in smokers who develop precancerous lesions that almost always resolve. We now have a model to study the driver mutations that take precancerous lesions to invasive squamous lung cancer and with this model we can start to identify novel therapies to prevent the development of precancerous lesions and/or progression of precancerous lesions. We also developed a model of precancerous lesions in a dish which allows us to screen for compounds that promote or resolve these premalignant lesions. Our overall goal is to use these models to develop a targeted chemoprevention strategy for squamous lung cancer.