The lung is a great challenge to oncologists and is where lethal human cancers develop more frequently than in any other organ site. Two large, expensive chemoprevention trials, the Alpha-Tocopherol and Beta-Carotene (ATBC) study and Beta-Carotene and Retinol Efficacy Trial (CARET), highlight the intractability of the lung thus far to effective cancer prevention (1, 2). Both of these prevention trials suggested neutral or harmful results (by primary analyses) in a combined population of more than 47,000 smokers who were followed up to 10 years. The large size and long duration of these trials reflect, in part, the limitation of smoking as the primary risk eligibility criterion; their inefficacy may reflect the limitations of the commonly used nontargeted agents (vitamin E, β-carotene, and retinol). These limitations may be overcome by molecular research designed (a) to identify the highest risk subgroups among smokers, which would in turn allow...

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