Abstract IA20: Targeted lung cancer chemoprevention through reverse migration

Abstract

Abstract The hypothesis that lung cancer can be prevented with agents selected on the basis of epidemiologic data has, unfortunately, been disproven in many large randomized trials conducted in the last 25 years. The results of these trials have overwhelmingly demonstrated not only the lack of benefit of most chemopreventive agents selected in this manner but also, importantly, the harmful effects of some of these agents in subsets of patients including current smokers. Despite limited progress in the multimodality treatment of lung cancer, the cure rate for this disease is very disappointing; however, more recent discoveries of molecular “driver mutation” targets in lung cancer and treatment approaches with “matched” targeted agents in selected patient cohorts has been highly promising. This latter approach demonstrates that progression of even heterogeneous cancers can be intercepted by “molecularly relevant” targeted agents for the treatment of advanced disease. A proposed new strategy for lung cancer prevention, therefore, is to apply a “reverse migration” of agents from the advanced disease to the chemopreventive setting; that is, to first identify the molecular drivers in the premalignant target tissue, and then to match these “hallmark” changes with molecularly targeted agents seen to be effective in advanced disease. This approach can be applied in the adjuvant as well as prevention settings, as has been demonstrated by the use of tamoxifen in breast cancer. Thus, the major points I am going to present include the current landscape of chemoprevention in lung cancer and a new strategy of “reverse migration” for future chemoprevention trials in the 21st century.