The impact of multiple drug resistance (MDR) proteins on chemotherapy and drug discovery.
Transportation of molecules across the cell membrane in living organisms is a critical aspect of life. Transportation includes importation of nutrients from the environment and exportation of toxic compounds. When export includes therapeutic compounds, then the practice of clinical medicine may become compromised. Often efflux of therapeutic compounds is mediated by a large superfamily of proteins referred to as multidrug resistance (MDR) proteins. The initial sections of this chapter are focused on MDR proteins and their negative impact on clinical medicine in cancer chemotherapy as well as infectious diseases mediated by bacteria, fungi and parasites. A brief description of major classes of MDR proteins found in microbes is followed by a more exhaustive treatment of ABC transporters in lower eukaryotes and parasites as well as cancerous mammalian cells. Later sections deal with potential and real positive aspects and applications brought about by a growing knowledge of MDR proteins. Examples described include improved antibiotic production, leveraging MDR proteins in drug discovery, new therapeutic options, dual therapy in treatment of cancer and infectious diseases, and finally MDR proteins as targets for new classes of therapeutic compounds.
Skatrud
Paul L
PL
Elanco Animal Health Science, Eli Lilly and Company, Greenfield, Indiana 46140, USA. Skatrud_Paul_L@Lilly.com
D000818:Animals; D001419:Bacteria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm; D004358:Drug Therapy / Q000639:trends*; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology; D005658:Fungi / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology; D010271:Parasites / Q000187:drug effects / Q000235:genetics; D010272:Parasitic Diseases / Q000188:drug therapy
D001426:Bacterial Proteins; D005656:Fungal Proteins; D009363:Neoplasm Proteins