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Drug resistance molecules: lessons from oncology
George L Scheffer1, Rik J Scheper
1Department of Pathology, Free University Medical Center, Amsterdam, The Netherlands.
Novartis Foundation Symposium
|May 7, 2002
Summary
Researchers developed monoclonal antibodies to study multidrug resistance (MDR) in cancer. These antibodies target proteins like P-glycoprotein and BCRP, aiming to understand their role in drug resistance and normal physiology.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Multidrug resistance (MDR) is a major challenge in cancer chemotherapy.
- MDR is often linked to the overexpression of specific transporter proteins that reduce intracellular drug concentrations.
Purpose of the Study:
- To generate monoclonal antibodies against key MDR-associated proteins.
- To investigate the role of these proteins in clinical drug resistance.
- To explore the presence and function of these proteins in normal human tissues.
Main Methods:
- Development of monoclonal antibodies targeting MDR-associated proteins (e.g., P-glycoprotein, MRPs, BCRP, lung-resistance protein/major vault protein).
- Application of antibodies in studies of clinical drug resistance.
- Immunohistochemical analysis of normal human tissues.
Main Results:
- Successfully generated monoclonal antibodies recognizing multiple MDR-associated proteins.
- Antibodies are being used to elucidate the specific roles of these proteins in cancer drug resistance.
- Initial studies explore the expression patterns of these proteins in normal human physiology.
Conclusions:
- Monoclonal antibodies provide a valuable tool for studying MDR.
- Further research will clarify the contribution of distinct MDR transporters to clinical resistance and normal biological functions.
- Understanding these molecular mechanisms may lead to improved cancer therapies.