Mechanism of resistance to anthracyclines and vinca alkaloids.
Occurrence of cross-resistance between anthracyclines and vinca alkaloids is the rule in experimental tumors with acquired resistance to these drugs. So far, there is no indication that this phenomenon is due to an intracellular mechanism of action common to the two groups of drugs. In nearly all reported studies, acquired experimental resistance and cross-resistance are related to a decreased cellular accumulation of both types of drugs, although other factors also are involved. In Ehrlich ascites tumors, a number of findings at steady-state conditions indicate that the decreased accumulation is dependent on a cellular mechanism for active outward drug transport, which is common to anthracyclines and vinca alkaloids, but changes in inward transport and intracellular binding capacity also contribute. Similar findings have been reported for resistance and cross-resistance in P388 leukemia. Recent results with counteraction of acquired experimental resistance in animal tumors by inhibition of outward drug transport and studies on the effect of different anthracycline derivatives on accumulation of daunomycin in resistant cells are discussed.
D000818:Animals; D000903:Antibiotics, Antineoplastic; D001693:Biological Transport, Active; D004351:Drug Resistance; D006801:Humans; D009279:Naphthacenes / Q000378:metabolism / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D014748:Vinca Alkaloids / Q000378:metabolism / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D009279:Naphthacenes; D014748:Vinca Alkaloids