Targeted therapies for the prevention of lung cancer

Abstract

Lung cancer is a leading cause of mortality and morbidity in industrialized countries and potentially one of the most preventable cancers. The major cause of this neoplasm, cigarette smoking, has been well established since the 1950s. Legislative, regulatory and educational efforts have resulted in significant reductions in the number of smokers, decreasing the percentage of individuals who initiate the smoking habit and increasing the number of persons who quit. Nevertheless, there is wide recognition of the need to address the issue of lung cancer prevention for those who are addicted to cigarettes or who are exposed to lung carcinogens in other ways. Strategies for smoking cessation now include nicotine replacement, and modulation of central nervous system addictive mechanisms through neuropharmacology. For those who have experienced prolonged carcinogen exposure a growing number of novel strategies based on epidemiologic observations as well as oncologic principles are under investigation. Many promising avenues have been proposed and while no agent is yet approved as chemopreventive for lung cancer a growing number of these agents are being tested as primary, secondary and tertiary prevention strategies. Proposed primary prevention strategies include cigarette abstinence and treatment of cigarette addiction, using appropriate cancer screening methods, decreasing environmental exposure, and possibly vaccination. Proposed secondary prevention strategies include methods for smoking cessation, lifestyle and diet modification, and modulation of molecular pathways that lead to lung cancer. Proposed tertiary prevention strategies include individually tailored therapies against certain molecular pathways as well as treatments to minimize disease metastasis and its sequelae. Currently, treatment for nicotine addiction includes nicotine replacement and medications such as bupropion and the recently approved varenicline. Attempts to modify the development of lung cancer have included the use of nutritional supplements such as beta-carotene, selenium, vitamin E and vitamin A. Conventional medications have also been suggested, including cyclooxygenase-2 inhibitors, aspirin and statins. Newer therapies that are being investigated for their potential preventative role against lung cancer include epidermal growth factor receptor inhibitors, monoclonal antibodies, tyrosine kinase inhibitors, farnesyl transferase inhibitors, peroxisome proliferator-activated receptor agonists, cell cycle inhibitors, and demethylating agents. This review discusses lung cancer, screening, and many of the different agents currently being investigated for their role in the prevention of this disease.