Multidrug resistance in human tumors—molecular diagnosis and clinical significance

Abstract

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. This review describes these drug resistance genes and techniques for detection and quantification of their expression and function. Because these markers have clinical significance and usefulness, currently available technology warrants the application of these markers in clinical oncology.