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Chemoprevention of Lung Cancer: Prospects and Disappointments in Human Clinical Trials
Division of Pulmonary, Critical Care, and Sleep Medicine, Departments of Medicine and Environmental Medicine, New York University School of Medicine, New York, NY 10016, USA
* Author to whom correspondence should be addressed.
Received: 6 December 2012; in revised form: 15 January 2013 / Accepted: 17 January 2013 / Published: 24 January 2013
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.
Keywords: lung cancer; chemoprevention; antioxidants; anti-inflammatories; carcinogenesis; biomarkers
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MDPI and ACS Style
Greenberg, A.K.; Tsay, J.-C.; Tchou-Wong, K.-M.; Jorgensen, A.; Rom, W.N. Chemoprevention of Lung Cancer: Prospects and Disappointments in Human Clinical Trials. Cancers 2013, 5, 131-148.
Greenberg AK, Tsay J-C, Tchou-Wong K-M, Jorgensen A, Rom WN. Chemoprevention of Lung Cancer: Prospects and Disappointments in Human Clinical Trials. Cancers. 2013; 5(1):131-148.
Greenberg, Alissa K.; Tsay, Jun-Chieh; Tchou-Wong, Kam-Meng; Jorgensen, Anna; Rom, William N. 2013. "Chemoprevention of Lung Cancer: Prospects and Disappointments in Human Clinical Trials." Cancers 5, no. 1: 131-148.