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

Various mechanism of antitumour drug transport across cell membranes has been described. Particular attention has been paid to a passive transport, active transport and multidrug resistance of complexes contained in antitumour 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 across the membrane is usually intermediated by means of a specific receptor or a carrier in that membrane, which facilitates the transport of compounds to and from the cell. Some drugs, e.g. doxorubicin and annamycin, can pass across the membrane by intermediacy of liposomes which exhibit a great activity in penetrating into tumour cells. The efficiency of antitumour drugs is limited by the appearance of resistance, i.e. by the lack of sensitivity of the cell to the administered drug. The presence in the membrane of specific proteins belonging to the ABC carriers group is postulated in a resistance theory; they would be responsible for 'pumping out' lipophilic drug molecules from the cell. Participation of high-energy ATP molecule is required by P-glycoprotein (Pgp) and by MRP protein described in this paper for their action. The mechanisms that are responsible for the cell resistance to drugs have been presented by analysing the resistance to antimetabolites, particularly to folate and fluoropyrimidine analogues, to alkylating agents, e.g. cisplatinum, and to heterocyclic compounds being responsible for so-called multidrug resistance.