Molecularly targeted approaches to the chemoprevention of lung cancer

Clin Cancer Res. 2004 Jun 15;10(12 Pt 2):4249s-4253s. doi: 10.1158/1078-0432.CCR-040019.


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.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor
  • Chemoprevention / methods*
  • Chemoprevention / trends*
  • Disease Progression
  • Enzyme Inhibitors
  • ErbB Receptors / drug effects
  • ErbB Receptors / physiology
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / prevention & control*
  • Randomized Controlled Trials as Topic
  • Receptors, Retinoic Acid / biosynthesis
  • Receptors, Retinoic Acid / physiology
  • Signal Transduction*
  • Up-Regulation


  • Biomarkers, Tumor
  • Enzyme Inhibitors
  • Receptors, Retinoic Acid
  • retinoic acid receptor beta
  • ErbB Receptors