This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hirsch, F. R. Articles by Lippman, S. M. Search for Related Content PubMed PubMed Citation Articles by Hirsch, F. R. Articles by Lippman, S. M.

Advances in the Biology of Lung Cancer Chemoprevention

Fred R. Hirsch, Scott M. Lippman

From the University of Colorado Cancer Center, Aurora, CO; and Departments of Thoracic/Head & Neck Medical Oncology and Clinical Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, Houston, TX

Address reprint requests to Fred R. Hirsch, MD, PhD, University of Colorado Cancer Center, 12801 E. 17th Avenue, POB 6511, Mail 8111, Aurora, CO 80010; e-mail: Fred.Hirsch{at}uchsc.edu.

The heavy burden of lung cancer, which includes the highest worldwide mortality of any cancer, and its resistance to standard approaches (smoking cessation, screening, and therapy), have motivated an intense interest in chemoprevention of this disease. Randomized controlled trials of agents (including retinoids, beta-carotene, and vitamin E) to prevent lung cancer have produced only disappointing clinical results to date. New, molecular-targeted approaches are advancing rapidly, however, with many promising targets and interactive signaling pathways for developing novel agents and combinatorial approaches in this setting. This promise is illustrated by recent studies of 15-hydroxyprostaglandin dehydrogenase, which plays a critical role in polyunsaturated fatty acid metabolism and (like another important target, prostacyclin) is downstream of cyclooxygenase-2. 15-hydroxyprostaglandin dehydrogenase degrades prostaglandin E₂, appears to have tumor suppressor activity, and can be induced both by peroxisome proliferator-activated receptor-gamma ligands and an epidermal growth factor receptor inhibitor. Other important targets/pathways include the insulin-like growth factor axis, phosphoinositide 3-kinase pathway, cyclin D and E family members, and epigenetic events. Defining highest lung cancer risk (eg, establishing molecular risk models through long-term analyses of high-risk cohorts) will facilitate the clinical development of molecular-targeted prevention that will potentially reduce the enormous burden of lung cancer.

Supported in part by grant CA16672 (The University of Texas M. D. Anderson Cancer Center Support Grant) from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

This article has been cited by other articles:

				F. R. Khuri and D. M. Shin Head and Neck Cancer Chemoprevention Gets a Shot in the Arm J. Clin. Oncol., January 20, 2008; 26(3): 345 - 347. [Full Text] [PDF]

				S. M. Lippman and J. V. Heymach The Convergent Development of Molecular-Targeted Drugs for Cancer Treatment and Prevention Clin. Cancer Res., July 15, 2007; 13(14): 4035 - 4041. [Abstract] [Full Text] [PDF]

				C. P. Schroeder, H. Kadara, D. Lotan, J. K. Woo, H.-Y. Lee, W. K. Hong, and R. Lotan Involvement of Mitochondrial and Akt Signaling Pathways in Augmented Apoptosis Induced by a Combination of Low Doses of Celecoxib and N-(4-Hydroxyphenyl) Retinamide in Premalignant Human Bronchial Epithelial Cells Cancer Res., October 1, 2006; 66(19): 9762 - 9770. [Abstract] [Full Text] [PDF]

				F. Kamangar, G. M. Dores, and W. F. Anderson Patterns of Cancer Incidence, Mortality, and Prevalence Across Five Continents: Defining Priorities to Reduce Cancer Disparities in Different Geographic Regions of the World J. Clin. Oncol., May 10, 2006; 24(14): 2137 - 2150. [Abstract] [Full Text] [PDF]

				J. E. Celis, P. Gromov, J. M. A. Moreira, T. Cabezon, E. Friis, I. M. M. Vejborg, G. Proess, F. Rank, and I. Gromova Apocrine Cysts of the Breast: Biomarkers, Origin, Enlargement, and Relation with Cancer Phenotype Mol. Cell. Proteomics, March 1, 2006; 5(3): 462 - 483. [Abstract] [Full Text] [PDF]

				A. L. Sabichi, X. Xu, and S. M. Lippman RAR{beta}1': Primed To Fight Retinoid Resistance in Lung Carcinogenesis J Natl Cancer Inst, November 16, 2005; 97(22): 1632 - 1633. [Full Text] [PDF]