MULTIDRUG-RESISTANCE - MOLECULAR AND CLINICAL ASPECTS

Clinical drug resistance, a common and compromising side-effect during anticancer chemotherapy, is an acquired cellular resistance simultane ously to several cytotoxic drugs. Expression of the multidrug resistan ce gene (mdr) is one of the most-studied potential underlying mechanis ms. 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 glycop rotein that, on the basis of its structure, is considered to act as a drug-efflux pump excreting various drugs from cells. The human mdr1 ge ne is thus a major regulated gene playing an important role in the mol ecular mechanism of multidrug resistance. Its bipartite structure of t wo similarly organized halves is explained by a gene fusion event duri ng evolution. However, the clinical significance of this particular fe ature, if it seemed obvious in the 1980s as a factor producing chemore sistance, is currently revised - being a marker of tumor aggressivenes s rather than the cause of drug resistance.