MULTIDRUG-RESISTANCE GENES (MRP) AND MDR1 EXPRESSION IN SMALL-CELL LUNG-CANCER XENOGRAFTS - RELATIONSHIP WITH RESPONSE TO CHEMOTHERAPY

Intrinsic or acquired drug resistance is a major limiting factor of th e effectiveness of chemotherapy. Increased expression of either the MR P gene or the MDR1 gene has been demonstrated to confer drug resistanc e in vitro. In this study, we examined MRP and MDR1 gene expression in a panel of 17 small cell lung cancers (SCLC) xenografted into nude mi ce from treated and untreated patients using an RT-PCR technique. For some of them, the outcome of the corresponding patients was known and we related MDR1/MRP expression with the xenograft response to C'CAV (c yclophosphamide, cisplatin, adriamycin and etoposide) combined chemoth erapy. Fifteen (88%) of the 17 cases of SCLC were found to be positive for either MDR1 or MRP, MRP gene expression was present in 12 (71%) o f 17 cases, whereas MDR1 gene expression was detected in eight (50%) o f 16 cases. For six SCLC, the survival duration of patients differed, with three patients surviving for more than 30 months after therapy. A mong these six tumours, five expressed MRP and/or MDR1. These six xeno grafts responded to the C'CAV treatment but a significant rate of cure was obtained in only three cases. No obvious relationship was observe d between the response to this treatment and MRP or MDR1 expression. H owever, the remarkably high levels and frequency of MRP expression in some SCLC samples indicate that future developments in chemotherapy of this tumour type should anticipate that drugs which are substrates of MRP may be of limited effectiveness. (C) 1998 Elsevier Science Irelan d Ltd. All rights reserved.