Abstract
Numerous epidemiological studies have consistently linked the presence of chronic obstructive pulmonary disease (COPD) to the development of lung cancer, independent of cigarette smoking dosage. The mechanistic explanation for this remains poorly understood. Progress toward uncovering this link has been hampered by the heterogeneous nature of the two disorders, with each being characterized by multiple sub-phenotypes of disease.
COPD can be broadly split into two disease processes, disease of the breathing tubes (airways disease) or destruction of the tiny air-sacks in the peripheral regions of the lung (airspace disease, or emphysema). A few insightful clinical studies have more clearly illustrated the nature of the link between COPD/emphysema and lung cancer by demonstrating that lung cancer risk is conferred by the emphysema component, and not by the airway component.
The current onus on the field is to identify mechanisms of disease common to both emphysema and lung cancer. There are several possibilities, including common genetic susceptibilities, competing forces with respect to apoptotic signaling, and shared inflammatory cell infiltrates.
The characteristic inflammatory cell infiltrate that is operative in emphysema pathogenesis and present within the tumor microenvironment, would appear to be the “low hanging fruit.” As such, this possible mechanistic link has received the most attention in this burgeoning field. Cigarette smoking produces a well-described infiltrate of macrophages, neutrophils, and T lymphocytes. Many of the products released by these cells'proteinases, reactive oxygen species, growth factors'are well known to fuel lung tumor growth, and in some cases, invasiveness as well. This microenvironment is not at all straightforward, however, as CD8+ T cells, present in emphysema, typically function in an antitumor fashion.
Going forward, the advancement of this field will require an improvement in disease models that allow for the simultaneous study of lung carcinogenesis within an emphysematous microenvironment. However, the potential to identify a common chemo-preventive target exists, and would be a welcome addition to clinicians, who have precious few options for patients afflicted with one or both of these diseases.
Citation Format: A. McGarry Houghton. Inflammation links COPD/emphysema and lung cancer. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr CN01-01.
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