Testing for tumor drug resistance in the age of molecular medicine. A contribution to the Debate Round-Table on phenotypic and genotypic analyses of multidrug resistance (MDR) in clinical hospital practice

Abstract

The detection of multidrug resistance (MDR) in clinical hospital practice represents an important strategy to combat clinical tumor drug resistance. Predicting the response of tumors to cytostatic drugs is of prognostic value. The ‘Debate Round-Table on Phenotypic and Genotypic Analyses of Multidrug Resistance (MDR) in Clinical Hospital Practice’ was launched in 1997 to address specific questions on this topic. The results published thus far are a rich source to learn about the promises and pitfalls of methods, eg surrogate and functional tests and protein or mRNA expression assays as well. In the present paper, some requirements are discussed for applications of drug resistance testing in clinical routine diagnostics. To improve the detection of low-level resistance, established methodologies may be strengthened with respect to: (1) standardization of sample handling, antibodies, PCR primers, and detection reagents; (2) standardization of protocols and far reaching automation in performance and evaluation of results to ensure high quality control criteria. Sophisticated new techniques will feature: (1) high-throughput analyses for the ‘horizontal screening’ of single drug resistance genes in large numbers of patient samples at economically fair costs; (2) ‘vertical screening’ of a large number of resistance mechanisms operating upstream or downstream of the actual drug–target interaction sites, in order to detect more complex and multifaceted genotypes and phenotypes of multidrug resistance.