Drug resistance limits the clinical efficacy of anticancer drugs in lung cancer which frequently shows intrinsic (non-small-cell lung cancer) or acquired (small-cell lung cancer) drug resistance. Several mechanisms of drug resistance are present in lung cancer cells. The expression of the MDR1 gene occurs to various degrees. The multidrug resistance-associated protein is also present in lung cancer cells. Enhanced activities of gluta-thione S-transferases and elevated glutathione levels of tumor cells may contribute to the intrinsic resistance of non-small-cell lung cancer. Alterations in topoisomerase II activity may also be involved in drug resistance. More recently, expression of the HER-2/neu oncogene or mutations of the p53 tumor suppressor gene were found to be associated with drug resistance, and gene therapy trials with transfer of wild-type p53 into lung cancer cells have been initiated. Thus, drug resistance in lung cancer is a complex phenomenon involving several mechanisms although their quantitative contribution to clinical drug resistance remains to be determined. Only knowledge of all clinically relevant drug resistance mechanisms might eventually lead to new treatment strategies and, thereby, improve the outcome of chemotherapy in lung cancer patients.

Keywords:
Lung cancer, Drug resistance, Multidrug resistance, P-glycoprotein, MDR1 gene, MRP, p53, HER-2/neu
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© 1997 S. Karger AG, Basel
1997
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