Advances in the Molecular Detection of ABC Transporters Involved in Multidrug Resistance in Cancer

Jean-Pierre      Gillet; Michael      M. Gottesman

Abstract

ATP-Binding Cassette (ABC) transporters are important mediators of multidrug resistance (MDR) in patients with cancer. Although their role in MDR has been extensively studied in vitro, their value in predicting response to chemotherapy has yet to be fully determined. Establishing a molecular diagnostic assay dedicated to the quantitation of ABC transporter genes is therefore critical to investigate their involvement in clinical MDR. In this article, we provide an overview of the methodologies that have been applied to analyze the mRNA expression levels of ABC transporters, by describing the technology, its pros and cons, and the experimental protocols that have been followed. We also discuss recent studies performed in our laboratory that assess the ability of the currently available high-throughput gene expression profiling platforms to discriminate between highly homologous genes. This work led to the conclusion that high-throughput TaqMan-based qRT-PCR platforms provide standardized clinical assays for the molecular detection of ABC transporters and other families of highly homologous MDR-linked genes encoding, for example, the uptake transporters (solute carriers- SLCs) and the phase I and II metabolism enzymes.

Keywords: ABC transporters, clinical diagnosis, personalized medicine, TaqMan-based qRT-PCR, cancer, chemotherapy, molecular diagnostic assay, high-throughput gene expression, highly homologous genes, MDR-linked genes, immune system, cystic fibrosis, pleiotropic mechanisms, Microarrays, cDNA Arrays