Lung cancer: Mechanisms of carcinogenesis by asbestos

Lung cancers have typically been reported in asbestos-exposed cohorts in smokers, and interactions between cigarette smoke and asbestos may be additive or multiplicative in the development of tumors. Research has indicated that some cellular and molecular events elicited by exposures to chemical carcinogens in cigarette smoke or asbestos fibers are different in lung epithelial cells, the target cells of lung carcinomas. We describe here contemporary concepts of lung cancer development and recent experimental studies providing an understanding of how asbestos and components of cigarette smoke act alone and together to cause lung cancers. We emphasize the importance of the tumor microenvironment including inflammation and fibrosis, interactions between different cell types in the lung that culminate in these events, and the role of epigenetics, a relatively new tool in understanding a number of common molecular events in carcinogenesis. Lastly, we provide a perspective on the multiple properties of different asbestos fiber types that may be critical in assessing their toxicity and carcinogenicity in lung tissue and the development of a quantitative model to predict the pathogenicity of mineral fibers in lung cancers.