Neuroendocrine tumors of the lung. Pathology and molecular biology.

Our understanding of the molecular genetic changes in lung cancer pathogenesis is advancing rapidly with several specific genes and chromosomal regions having been identified. As the biochemical functions of the proteins encoded by these genes are discovered, they appear to fall into several growth regulatory pathways. The large number of genetic lesions in clinically evident lung cancer has prompted searching for mutations in preneoplastic lung tissue before the pathologic evidence of cancer as a tool for early molecular diagnosis. In addition, these markers need to be rigorously assessed for their prognostic importance. Finally, understanding the molecular basis of lung cancer should allow "translation" of these findings from the bench to the bedside. These include very early molecular diagnosis, identification of persons at highest risk of developing lung cancer to allow for more effective smoking cessation strategies, chemoprevention, and very early treatment studies (clinical studies beginning); rational development of novel therapies such as immunization against tumor-specific mutant peptides (clinical studies ongoing); blocking the expression of activated oncogenes (such as with antisense or triple helix agents); and replacing defective tumor suppressor genes (clinical studies ongoing).