MULTIDRUG RESISTANCE TRANSPORTERS: BEYOND MDR1

摘要

ABC (ATP Binding Cassette) transporters, also called multidrug resistance transporters, are one of the most important causes of multidrug resistance in tumor cells. The ABC transporters belong to the ABC Superfamily of proteins, one of the largest known protein families. Members of this family are primarily active transport proteins that are expressed on cell membranes. In prokaryotes these proteins can serve import and export functions but in eukaryotic cells, only export functions have been described. The ABC transporter family contains over 40 members which have been subdivided into subfamilies (designated ABC 'A' through ABC 'G'). Members of these subfamilies participate in antigen presentation, cholesterol and lipid transport, mitochondrial homeostasis, regulation of several ion channels and multidrug resistance. Only 15 ABC transporters have been observed to export chemotherapy drugs, but most of these observations are limited to in vitro conditions. Only 3 members of the ABC transporter family have been shown to be relevant to clinical chemotherapeutic drug resistance in cancer patients: P-glycoprotein (P-gp), Multidrug resistance-related protein, and Breast Cancer Resistance Protein. Information gleaned from research in human tumor cell lines and cancer patients has, to date, been applicable to veterinary patients. Specifically, substrates for a particular ABC transporter in humans are also substrates for the canine and feline orthologues. Similarly, compounds that inhibit a particular ABC transporter in humans also appear to inhibit the orthologous canine and feline transporters. This article will briefly review the role of P-glycoprotein in canine and feline cancer patients (since this topic has been reviewed elsewhere) and will provide a more in-depth review of the literature regarding Multidrug resistance-related protein and Breast Cancer Resistance Protein in human as well as veterinary patients.