The potential contributions of chronic inflammation to lung carcinogenesis.
A number of lines of evidence suggests that chronic inflammation contributes to the process of carcinogenesis. In this article, this theme is explored with particular emphasis on the involvement of inflammation in the development of lung cancer. A number of molecular pathways activated in chronic inflammation may contribute to lung carcinogenesis. The challenge is to conceptualize a cohesive picture of this complex biology that allows for effective pharmaceutical intervention. Initial therapeutic efforts involve strategies to block single pathways, such as with cyclooxygenase (COX) activity. However, the more that is learned about the consequences of COX activity, the more evident are the relationships of this enzyme to other classes of regulatory molecules such as the potent nuclear factor-kB. In light of this emerging picture, more global intervention strategies, such as with drug combinations, may be essential for success. Further basic study is essential to sort out possible molecular relationships and to permit elucidation of the most critical regulatory circuits. Given the complexity of these molecular interactions, well-designed clinical trials that specifically evaluate the precise effects of particular antiinflammatory drugs on lung carcinogenesis will also be critical to sort out the complexity and to validate successful approaches to arresting lung carcinogenesis.
Department of Histology and Pathology, Center for Applied Medical Research, University of Navarra, Pamplona, Spain.
Santiago
S
Ballaz
James L
JL
Mulshine
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D002986:Clinical Trials as Topic; D004847:Epithelial Cells; D006801:Humans; D007249:Inflammation; D008175:Lung Neoplasms / Q000276:immunology* / Q000503:physiopathology*; D016328:NF-kappa B / Q000494:pharmacology; D009389:Neovascularization, Pathologic; D018384:Oxidative Stress; D011451:Prostaglandin-Endoperoxide Synthases / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D011451:Prostaglandin-Endoperoxide Synthases