Recent advances in genetics and molecular biology lead to the identification of genes and protein products overexpressed by tumors. Such products, called tumor markers, were previously used only as diagnostic and prognostic tools, but are currently being the target of extensive research, with growing evidence that some of them may have an important role in the development of new treatment modalities, targeting the tumor cell biological cycle. In this article, the authors review the role of some of the traditionally known tumor markers (CEA, p53, NSE, K-ras), and describe the prevalence and the role of the epidermal growth factor receptor (EGFR) overexpression and its protein product, p185neu. New drugs have been developed, aiming at the blockade of the signaling process initiated by the EGFR. Among these, the authors highlight ZD1839 (Iressa), a new orally administered drug that reversibly and selectively inhibits the EGFR tyrosine-kinase activity. This drug has demonstrated good results in the treatment of non-small-cell lung cancer, as an isolated drug or in combination with other chemotherapy agents. Targeting the EGFR could represent a significant contribution to cancer therapy, mainly the non-small-cell lung cancer.

Keywords: Lung neoplasms. Tumor markers. Receptor epidermal growth factor.

Objective: To study the effect of perillyl alcohol on the gene expression of human pulmonary adenocarcinoma cells. Methods: Pulmonary adenocarcinoma cells were incubated with perillyl alcohol in dilutions ranging from 0.03% to 0.0003% for 48 hours. Alterations were observed in the cell morphology, and cell viability was quantified using [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays. Protein synthesis of samples previously targeted with S35 was analyzed using electrophoresis on a polyacrylamide gel. Expression of the proteins p53 and p44/42 was determined using the Western blot method. Results: After 48 hours of incubation, greater numbers of morphological alterations were observed in cells treated with the 0.03% perillyl alcohol dilution than in those treated with perillyl alcohol diluted to 0.003% or further. Treatment with perillyl alcohol dilutions of 0.03%, 0.003% and 0.0003% inhibited cellular viability by 60.17% (p < 0.001), 15.62% (p < 0.001) and 11.53% (p < 0.05), respectively. The results show that 28-kDa, 42-kDa and 110-kDa proteins were induced. No statistically significant effect on p53 expression was observed. In comparison with the expression of a-tubulin, the 0.003% perillyl alcohol dilution induced an increase in p42 phosphorylation and a marked decrease in p44 phosphorylation. Conclusion: The results suggest that there are other, previously undescribed, metabolic pathways for perillyl alcohol effects in human pulmonary adenocarcinoma cells.

Keywords: Adenocarcinoma; Lung neoplasms; Monoterpenes; Cell culture; Lung/cytology