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Multidrug resistance in human tumors--molecular diagnosis and clinical significance
1Department of Pathology, Miami Children's Hospital, Research Institute, Miami, Florida 33155, USA.
Background:
Multidrug resistance (MDR) of human tumors is one of the major reasons for the failure of chemotherapy in refractory cancer patients. MDR can be intrinsic or acquired, depending on the time of its occurrence, either at diagnosis or during chemotherapy. Molecular investigations in MDR during the last two decades have resulted in the isolation and characterization of genes coding for P-glycoprotein, multidrug resistance-associated protein, lung resistance-related protein, drug resistance-associated protein, breast cancer resistance protein, and adenosine triphosphate-binding cassette protein. Several molecular probes, primer pairs, and monoclonal antibodies have been developed over these years to quantify the regulation and expression of these drug resistance markers in tumor cells. Methodologies have also been standardized to estimate the gene amplification, mRNA and protein expression, and functionality of drug resistance proteins in clinical specimens from cancer patients.
Methods And Results:
This review describes these drug resistance genes and techniques for detection and quantification of their expression and function.
Conclusions:
Because these markers have clinical significance and usefulness, currently available technology warrants the application of these markers in clinical oncology.
Insights
Multidrug resistance (MDR) in tumors hinders chemotherapy. This review details MDR genes and detection methods, highlighting their clinical utility in oncology.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Multidrug resistance (MDR) in human tumors is a primary cause of chemotherapy failure in refractory cancer patients.
- MDR can be intrinsic or acquired, manifesting either at diagnosis or during treatment.
- Extensive research has identified key genes involved in MDR, including those encoding P-glycoprotein, multidrug resistance-associated protein, and breast cancer resistance protein.
Purpose of the Study:
- To review drug resistance genes implicated in human tumors.
- To describe standardized techniques for detecting and quantifying the expression and function of these drug resistance markers.
Main Methods:
- Review of scientific literature on MDR genes.
- Description of methodologies for quantifying gene amplification, mRNA and protein expression, and protein functionality.
- Discussion of molecular probes, primer pairs, and monoclonal antibodies used for marker detection.
Main Results:
- Identification and characterization of multiple drug resistance genes.
- Standardization of techniques for assessing MDR markers in clinical specimens.
- Development of tools like molecular probes and antibodies for quantification.
Conclusions:
- The identified MDR markers possess significant clinical value.
- Current technologies support the application of these markers in clinical oncology for improved patient outcomes.