Rationale for Lung Adenocarcinoma Prevention and Drug Development Based on Molecular Biology During Carcinogenesis

Lung adenocarcinoma (LUAD) is the most common and aggressive subtype of lung cancer with the greatest heterogeneity and aggression. Inspite of recent years’ achievements in understanding the pathogenesis of this disease, as well as the development of new therapeutic approaches, our knowledge on crucial early molecular events during its development is still rudimentary. Recent classification and grading of LUAD has postulated that LUAD does not arise spontaneously, but through a stepwise process from lung adenomatous premalignancy atypical adenomatous hyperplasia to adenocarcinoma in situ, minimally invasive adenocarcinoma, and eventually frankly invasive predominant adenocarcinoma. In this review, we discuss the molecular processes that drive the evolutionary process that results in the formation of LUAD. We also describe how to handle lung premalignancy in clinical settings based on the most recent advances in genomic biology and our own understanding of lung cancer prevention.