Mechanisms of resistance to xenobiotics in human therapy.

Xenobiotic resistance is the major cause of failure in human therapies. Because of their serious clinical and economical consequences, resistance phenomena have been intensively studied in the case of antibacterial, anticancer, antipaludic and anti-human immunodeficiency virus-1 therapies. Beside pharmacological factors that can impede the action of the drugs, several cellular mechanisms of resistance have been described. Surprisingly, these mechanisms are conserved among bacteria, eucaryotic cells, parasites and viruses. The efficiency of drugs can be circumvented by alteration of the drug cellular concentration (altered influx, enhanced efflux or sequestration), detoxification, alteration of the drug target, nonactivation or inactivation of the drug, or by enhanced DNA repair.