MULTIDRUG-RESISTANT GENE-EXPRESSION IN SMALL-CELL LUNG-CANCER

The development of drug resistance can contribute to treatment failure in small-cell lung cancer(SCLC). In this report, we investigate p-gly coprotein-mediated multidrug resistance (MDR) in these patients. Tumor tissue was obtained prior to treatment and at relapse if possible, sh ort-term culture was carried out. and these tumor cells were analyzed for MDR gene expression by slot blot and reverse transcriptase polymer ase chain reaction (RT-PCR) and northern blot analysis. Three cell lin es were also established from shortterm cultures. Twenty-four patients with MDR(-) and seven with MDR+(++) were available for survival analy sis. Median survival for MDR(-) patients was 10 months, whereas for MD R+(++) patients it was 2 months. This was statistically significance ( p < 0.0007). The presence of MDR1 gene expression also correlated with the lack of response to chemotherapy (p < 0.001). Increased MDR1 gene expression is usually present in patients with more tumor burden at i nitial diagnosis. Furthermore, loss of MDR1 gene expression can occur in intrinsically MDR(+) SCLC cells after multiple passages in drug-fre e media. We concluded that increased MDR1 gene expression is present i n a small number of SCLC both before and after chemotherapy and usuall y signifies poor survival and no response to chemotherapy.