title: Molecularly targeted approaches to the chemoprevention of lung cancer.
abstract: Large, randomized trials have been conducted in the primary prevention of lung cancer using micronutrients or derivative agents for which epidemiological data suggested a potential role in lung cancer prevention. The disappointing primary prevention trials of beta-carotene, alpha-tocopherol, and retinyl palmitate have led to the development of a more compact, biomarker-driven series of translational trials of lung cancer prevention that target reversal of premalignancy as the primary end point. Serial trials of 13-cis-retinoic acid (isotretinoin) and other retinoids have failed to show a difference in reversal of premalignancy in active smokers or in second primary tumor prevention. However, a trial of 9-cis-retinoic acid, a pan retinoid/rexinoid agonist, showed up-regulation of retinoic acid receptor beta (RAR-beta), a potentially important intermediate marker of response in lung cancer premalignancy. Other planned or ongoing trials currently target important molecular markers of lung carcinogenesis and progression including cyclooxygenase-2, the ras-signaling pathway through farnesyl transferase inhibitors, and the tyrosine kinase/epidermal growth factor receptor pathway (gefitinib, erlotinib). Early results of bioadjuvant trials in head and neck cancer suggest that combination chemoprevention will ultimately be an important option.
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, Georgia, USA. fkhuri@emory.edu
authors.forename: Fadlo R
authors.initials: FR
authors.lastname: Khuri
authors.forename: Victor
authors.initials: V
authors.lastname: Cohen
mesh_terms: D014408:Biomarkers, Tumor; D018890:Chemoprevention / Q000379:methods* / Q000639:trends*; D018450:Disease Progression; D004791:Enzyme Inhibitors; D066246:ErbB Receptors / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis / Q000502:physiology; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D004791:Enzyme Inhibitors; D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta; D066246:ErbB Receptors