CELLULAR-DRUG RESISTANCE IN LUNG-CANCER

Drug resistance limits the clinical efficacy of anticancer drugs in lu ng cancer which frequently shows intrinsic (non-small-cell lung cancer ) or acquired (small-cell lung cancer) drug resistance. Several mechan isms of drug resistance are present in lung cancer cells. The expressi on of the MDR1 gene occurs to various degrees. The multidrug resistanc e-associated protein is also present in lung cancer cells. Enhanced ac tivities of glutathione S-transferases and elevated glutathione levels of tumor cells may contribute to the intrinsic resistance of non-smal l-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 t ransfer of wild-type p53 into lung cancer cells have been initiated. T hus, drug resistance in lung cancer is a complex phenomenon involving several mechanisms although their quantitative contribution to clinica l drug resistance remains to be determined. Only knowledge of all clin ically relevant drug resistance mechanisms might eventually lead to ne w treatment strategies and, thereby, improve the outcome of chemothera py in lung cancer patients.