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Amplification of the mdr1-gene is uncommon in recurrent ovarian carcinomas
T Schöndorf1, A Scharl, C M Kurbacher
1Department of Gynecology and Obstetrics, University of Cologne, Germany.
Abstract:
Ovarian carcinomas are known to rapidly develop drug resistance against chemotherapeutic agents. This phenomenon is often associated with the expression of pl70-glycoprotein. A high rate of transcription of the corresponding mdr1-gene in resistant tumors is reported. Amplification of the mdr1-gene has been observed in tumor cell lines exposed to cytotoxic drugs; however, significant information is lacking as to whether this holds true in clinical carcinomas. To fill this gap, we investigated the rate of gene amplification of the mdr1-gene in 63 recurrent ovarian carcinomas and we determined the resistance pattern of these cells using an ex vivo assay. The tumors showed varying ex vivo resistance patterns which did not correlate to clinical parameters. Amplification of the mdr1-gene was not observed in any of the cancer specimens. Therefore, we conclude that mdr1-gene amplification is not a common pathway for the development of chemoresistance in clinical ovarian carcinomas.
Insights
Drug resistance in ovarian cancer is common but not due to mdr1-gene amplification. This study found no mdr1-gene amplification in clinical ovarian carcinomas, suggesting alternative mechanisms for chemoresistance.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Ovarian carcinomas frequently develop resistance to chemotherapy.
- This resistance is often linked to P-glycoprotein (pl70) expression and mdr1-gene transcription.
- While mdr1-gene amplification is seen in drug-exposed cell lines, its role in clinical settings is unclear.
Purpose of the Study:
- To investigate mdr1-gene amplification in clinical ovarian carcinomas.
- To correlate gene amplification with ex vivo drug resistance patterns.
Main Methods:
- Analysis of 63 recurrent ovarian carcinoma specimens.
- Assessment of ex vivo drug resistance patterns.
- Detection of mdr1-gene amplification.
Main Results:
- Observed varied ex vivo drug resistance patterns.
- No correlation found between resistance patterns and clinical parameters.
- No instances of mdr1-gene amplification were detected in any tumor specimen.
Conclusions:
- mdr1-gene amplification is not a prevalent mechanism for chemoresistance in clinical ovarian carcinomas.
- Alternative pathways likely contribute to drug resistance in this cancer type.