Oncogenes in human lung cancer

Publisher Website
Google Scholar
Abstract
While the last 15 years have not yielded substantial improvements in the diagnosis and treatment of lung cancer, this same period has experienced an extraordinary expansion of our understanding of cancer initiation and progression. These investigations have provided strong support for a multistep mechanism of tumor induction and progression [ 1 , 2 ] that previously could only be inferred from experimental animal models and from epidemiologic analyses. This recent work has also revealed that, in many cases, the structural alterations of the same gene products (for example, myc and ras or p53 and Rb genes) might be critical steps in the genesis of a wide range of adult tumors of differing histologie origins. These observations blur the distinction for investigators focusing on specific cancer models, while at the same time offer the hope that advances in the understanding and treatment of any particular tumor type will have far broader implications. In addition, now that the genetic basis for lung cancer has been well established, we are witnessing a resurgence of interest in mechanisms of specific environmental carcinogens as tools for a new generation of cancer prevention strategies [ 3 ]. There is currently no doubt that the use of tobacco products is the single most important (although not the only) causative factor in the development of lung cancer [ 4 , 5 ], and as these patterns of abuse spread there will be a projected worldwide increase in the incidence of lung malignancies paralleling that seen in North America and Europe over the last 50 years. Therefore, the challenge in the immediate future will be to apply the molecular clues obtained from the laboratory into effective preventive and therapeutic applications. The purpose of this chapter is to review some of the more important experiments concerning the molecular genetics of lung cancer, focusing on the identification (and implications) of somatic mutations in a limited number of cellular genes referred to as either dominant or recessive oncogenes.