Mechanisms of transport across cell membranes of complexes contained in antitumour drugs

Various mechanism of antitumour drug transport across cell membranes has be en described. Particular attention has been paid to a passive transport, ac tive transport and multidrug resistance of complexes contained in antitumou r drugs. A drug supply to the target site depends on the blood circulation within the tumour, on characteristic drug diffusion in the tissue, and also on binding protein. The physiologic transfer of hydrophilic compounds acro ss the membrane is usually intermediated by means of a specific receptor or a carrier in that membrane, which facilitates the transport of compounds t o and from the cell. Some drugs, e.g. doxorubicin and annamycin, can pass a cross the membrane by intermediacy of liposomes which exhibit a great activ ity in penetrating into tumour cells. The efficiency of antitumour drugs is limited by the appearence of resistance, i.e. by the lack of sensitivity o f the cell to the administered drug. The presence in the membrane of specif ic proteins belonging to the ABC carriers group is postulated in a resistan ce theory; they would be responsible for 'pumping out' lipophilic drug mole cules from the cell. Participation of high-energy ATP molecule is required by P-glycoprotein (Pgp) and by MRP protein described in this paper for thei r action. The mechanisms that are responsible for the cell resistance to dr ugs have been presented by analysing the resistance to antimetabolites, par ticularly to folate and fluoropyrimidine analogues, to alkylating agents, e .g. cisplatinum, and to heterocyclic compounds being responsible for so-cal led multidrug resistance. (C) 2001 Elsevier Science B.V. All rights reserve d.