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Expression of several resistance mechanisms in untreated human kidney and lung carcinomas
Abstract:
Thirty human renal cell carcinomas and 94 non-small cell lung carcinomas of previously untreated patients were analyzed for the presence of P-glycoprotein, glutathione S-transferase-pi and topoisomerase II by means of immunohistochemistry. In the renal cell carcinomas investigated, two resistance markers were seen in 53% and three resistance markers in 36% of the cases. In only three tumors was one resistance mechanism observed. In the 94 non-small cell lung carcinomas 34% had two and 20% three resistance mechanisms, whereas 24% of the tumors revealed only one resistance mechanism. For determining the resistance of the tumors against drugs an in vitro short-term test was used. Only 12% of the sensitive lung tumors had more than one resistance mechanism, whereas 70% of the resistant tumors did. Thus a significant relationship exists between the resistance measured in vitro and the overexpression of P-glycoprotein or glutathione S-transferase-pi and the down-regulation of topoisomerase II.
Insights
Drug resistance in cancer is linked to specific protein markers. Overexpression of P-glycoprotein and glutathione S-transferase-pi, along with reduced topoisomerase II, significantly correlates with tumor resistance.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Drug resistance is a major challenge in cancer treatment.
- Identifying predictive markers for drug resistance is crucial for personalized therapy.
Purpose of the Study:
- To investigate the presence of P-glycoprotein, glutathione S-transferase-pi, and topoisomerase II in renal cell and non-small cell lung carcinomas.
- To determine the relationship between these markers and in vitro drug resistance.
Main Methods:
- Immunohistochemistry was used to analyze protein expression in 30 renal cell carcinomas and 94 non-small cell lung carcinomas.
- An in vitro short-term drug sensitivity test was employed to assess tumor resistance.
Main Results:
- A high percentage of renal cell carcinomas (53%) and non-small cell lung carcinomas (34%) exhibited two or more drug resistance markers.
- Resistant tumors showed a significant association with P-glycoprotein overexpression, glutathione S-transferase-pi overexpression, and topoisomerase II down-regulation.
- Sensitive lung tumors rarely had multiple resistance mechanisms (12%), while resistant tumors frequently did (70%).
Conclusions:
- The study establishes a significant correlation between specific molecular markers and drug resistance in renal cell and non-small cell lung carcinomas.
- These findings suggest that P-glycoprotein, glutathione S-transferase-pi, and topoisomerase II can serve as predictive biomarkers for drug resistance in these cancers.
- Understanding these resistance mechanisms can guide the development of targeted therapies and improve patient outcomes.