Genetic Events in the Pathogenesis of Lung Cancer

¹ The NCI-Navy Medical Oncology Division of Cancer Treatment, National Cancer Institute and Uniformed University of the Health Sciences, Naval Hospital, Bethesda, MD.

Human lung cancer is not generally thought of as a genetic disease. However, a variety of recent experimental evidence, summarized above, leads inextricably to the conclusion that lung cancer cells have accumulated a series of genetic changes ("initiating" events) which activate the dominantly acting cellular proto-oncogenes on the one hand, while another group of changes seems to inactivate a second class of genes, which appear to be recessive, referred to as deletion or tumor suppressor genes. Changes in both types of genes appear necessary for the malignant transformation of lung cancer. In addition, autocrine growth factors, and transcription factors regulated by tumor promoters are produced by lung cancer cells, both of which could also participate in "promoting" the development of lung cancer after "initiating" events. Thus, it appears inescapable that new prevention, detection, and treatment strategies for lung cancer must be directed against the products of these initiating and promoting events.