Abstract
Decreasing the risk of lung cancer, or preventing its development in high-risk individuals, would have a huge impact on public health. The most effective means to decrease lung cancer incidence is to eliminate exposure to carcinogens. However, with recent advances in the understanding of pulmonary carcinogenesis and the identification of intermediate biomarkers, the prospects for the field of chemoprevention research have improved dramatically. Here we review the most recent research in lung cancer chemoprevention—focusing on those agents that have been investigated in human clinical trials. These agents fall into three major categories. First, oxidative stress plays an important role in pulmonary carcinogenesis; and therefore, antioxidants (including vitamins, selenium, green tea extracts, and isothiocyanates) may be particularly effective in preventing the development of lung cancer. Second, inflammation is increasingly accepted as a crucial factor in carcinogenesis, and many investigators have focused on anti-inflammatory agents, such as glucocorticoids, NSAIDs, statins, and PPARγ agonists. Finally, the PI3K/AKT/mTOR pathway is recognized to play a central role in tobacco-induced carcinogenesis, and inhibitors of this pathway, including myoinositol and metformin, are promising agents for lung cancer prevention. Successful chemoprevention will likely require targeting of multiple pathways to carcinogenesis—both to minimize toxicity and maximize efficacy.
Highlights
Lung cancer is the most common cause of cancer death world-wide
When selenium was investigated for the prevention of skin cancer in a randomized, double-blind, placebo-controlled trial that included over 1,300 patients, the investigators found that the subjects who received 200 mcg selenium supplementation for 4.5 years had a 44% decrease in lung cancer incidence [34]
Many other strategies and agents have been investigated for lung cancer chemoprevention, though most have not progressed to the human clinical trial stage
Summary
Lung cancer is the most common cause of cancer death world-wide This remains true, despite advances in the understanding of the molecular carcinogenesis and the development of new targeted therapies. In an attempt to decrease this high mortality rate, much attention has been devoted to developing methods for early detection of the disease, when it is at a more treatable stage. Many ongoing studies are looking at non-invasive biomarkers for early detection that could be combined with CT screening to decrease mortality even further. These methods may result in improved lung cancer survival; no screening program can succeed at detecting early stage cancer with 100% sensitivity and specificity. Decreasing the risk of lung cancer—or preventing its development in high-risk individuals—would be an even loftier goal
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