Multidrug resistance: molecular and clinical aspects.
Clinical drug resistance, a common and compromising side-effect during anticancer chemotherapy, is an acquired cellular resistance simultaneously to several cytotoxic drugs. Expression of the multidrug resistance gene (mdr) is one of the most-studied potential underlying mechanisms. The human mdr gene family encompasses two homologous members, the first of which, called the mdr1 gene, is the best-characterized so far. The human mdr1 gene has been shown to encode a membrane P-170 glycoprotein that, on the basis of its structure, is considered to act as a drug-efflux pump excreting various drugs from cells. The human mdr1 gene is thus a major regulated gene playing an important role in the molecular mechanism of multidrug resistance. Its bipartite structure of two similarly organized halves is explained by a gene fusion event during evolution. However, the clinical significance of this particular feature, if it seemed obvious in the 1980s as a factor producing chemoresistance, is currently revised-being a marker of tumor aggressiveness rather than the cause of drug resistance.
Dicato
M
M
Centre Hospitalier de Luxembourg.
Duhem
C
C
Pauly
M
M
Ries
F
F
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000494:pharmacology; D005075:Biological Evolution; D002986:Clinical Trials as Topic; D003001:Cloning, Molecular; D018432:Drug Resistance, Multiple / Q000235:genetics*; D015870:Gene Expression; D019450:Genes, MDR; D006801:Humans; D005810:Multigene Family; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D011379:Prognosis
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1