Abstract
The history of lung cancer chemoprevention trials has been uniformly disappointing in that the large phase III studies showed no effect or harm in actively smoking participants, and smaller phase II studies have also been negative. In this issue of the journal (beginning on page 793), Keith and colleagues report their randomized, placebo-controlled trial of the oral prostacyclin analogue iloprost, the first trial to show an improvement in bronchial histology (i.e., regression), which occurred in former, but not current, smokers with sputum atypia. This Perspective discusses the strength of the clinical signal provided by this observation and its implications for further drug development.