Javier Milara and Julio Cortijo Pages 3901 - 3938 ( 38 )
Cigarette smoking is the most recognized risk factor for many inflammatory diseases such as cardiovascular diseases, chronic obstructive pulmonary disease and for a number of malignances such as lung cancer. Lung cancer is currently considered the leading cause of cancer-related deaths because its aggressive nature and the lack of effective therapeutic options. Recent advances in molecular biology and immunology have improved the knowledge on different mechanisms implicated in lung cell malignant transformation, progression and metastasis, thus presenting an exciting new era for lung anticancer therapies. The way by which cigarette smoke may induce lung malignancy includes a large number of different mechanisms and substances, most of them currently unknown. Thus, identified carcinogenic compounds of cigarette smoke may induce themselves a direct cytotoxicity and mutagenic action on lung epithelial cells by means of generation of somatic mutations, epigenetic events, epithelial cell to mesenchymal cell transformations, as well as by chronic cell damage. However, the fact that there is a relative high prevalence of ex-smoker who may develop lung cancer after years of smoking cessation suggest that other causes are also implicated. Thus cigarette smoke-induced chronic lung inflammatory microenvironment, oxidative stress and cell structural alterations such as the increase of cell proliferation, angiogenesis and apoptosis arrest are irreversible processes that have a high influence in lung tumor growth. In this review we focused in current knowledge on the mechanisms implicated in cigarette smoke-induced lung chronic inflammatory processes leading to lung carcinogenesis, as well as in current therapies based on novel molecular advances.
Cigarette smoke, inflammation, lung cancer, cardiovascular diseases, chronic obstructive pulmonary disease, malignant transformation, progression, metastasis, cytotoxicity, mutations.
Unidad de Investigacion Clinica; Fundacion de Investigacion, Consorcio, Hospital General Universitario, Avenida Tres Cruces no 2, E-46014 Valencia, Spain.