Molecular approaches to lung cancer evaluation

The stagnation of therapeutic results in lung cancer over the last decade(s) is a matter of great concern, also due to the constantly increasing incidence of the disease. Among the reasons for this failing therapeutic progress is the lack of understanding of the molecular mechanisms underlying the disease. Presently molecular biology techniques contribute to the deciphering of these mechanisms. This review article gives an overview of the actual situation. The genetic changes leading to malignancy are successively considered at the DNA, RNA and protein levels. Alterations at the DNA level represent the bulk of the available data, being related to p53 mutations, alterations in the beta-tubulin gene, microsatellite alterations, methods for identifying individual and isolated aberrant cells, identification of epigenetic mechanisms such as methylation of the promoter region of tumor suppressor genes; alterations in pre-neoplastic lesions are also evoked. In all cases, the techniques are described and results presented. RNA based methods are critically considered, and the yeast functional assay described. Protein based methods are also considered. The use of cDNA microarrays opens new perspectives and brings the simultaneous identification of numerous DNA alterations at a grip, with hopefully significant improvements in treatment results and increased efficiency for early detection and prevention.