Premalignant lesions of squamous cell carcinoma of the lung: The molecular make-up and factors affecting their progression

Squamous cell carcinoma (SCC), one of the most common forms of lung cancer, shows accelerated progression and aggressive growth and usually is observed at advanced stages. SCC originates from morphological changes in the bronchial epithelium that occur during chronic inflammation: basal cell hyperplasia, squamous metaplasia, and dysplasia I-III. However, the process is not inevitable; it can be stopped at any stage, remain in the stable state indefinitely and either progress or regress. The reasons and mechanisms of different scenarios of the evolution of premalignant lesions in the respiratory epithelium are not fully understood. In this review, we summarized the literature data (including our own data) regarding genetic, epigenetic, transcriptomic and proteomic profiles of the premalignant lesions and highlighted factors (environmental causes, inflammation, and gene polymorphism) that may govern their progression or regression. In conclusion, we reviewed strategies for lung cancer prevention and proposed new models and research directions for studying premalignant lesions and developing new tools to predict the risk of their malignant transformation.