Chemoprevention of lung cancer

Abstract

CHEMOPREVENTION The chemoprevention of lung cancer is a major challenge for health care providers and researchers, but it also presents a significant opportunity for reducing lung cancer morbidity and mortality. Chemoprevention strategies can be applied to those at high risk, such as current or former smokers, and to those who have survived earlystage non-small cell lung cancer (NSCLC) but are at risk for second primary tumors. Many agents are being studied for chemopreventive activity. The most widely studied compounds are retinoids. These are a group of natural and synthetic vitamin A analogs that have been shown in animal models to suppress carcinogenesis and to affect the growth and differentiation of normal, premalignant, and malignant epithelial cells in vitro and in vivo. These agents work through a group of nuclear receptors that are part of the steroid and thyroid hormone receptor family. These receptors selectively regulate gene transcription, thereby regulating cell differentiation and proliferation. ~ Specific retinoid compounds studied in clinical trials include isotretinoin (13-cis-retinoic acid), etretinate, and retinol (retinyl palmitate). Their administration is associated with dose-related skin toxicity, which is reversible but often limits their use. In epidemiologic studies, dietary i~-carotene intake has been shown to be inversely correlated with lung cancer risk. 2 i~-Carotene is thought to function as an electron-scavenging antioxidant. 3 Vitamin E intake has also been associated with decreased incidence of cancer at several sites. 4 This vitamin also acts as an antioxidant. N-acetylcysteine is an aminothiol cysteine derivative and a precursor of glutathione. Glutathione plays a role in the detoxification of reactive electrophiles and free radicals through conjugation or reduction reactions. N-acetylcysteine has been shown in animal models to have preventive activity against many carcinogenic agents? Aspirin and other nonsteroidal antiinflammatory compounds are 266