[Significance of multidrug resistance in the therapy of malignant tumors].
Some human malignant tumours respond poorly to initial chemotherapy, indicating that they possess intrinsic resistance. On the other hand, in a significant portion of tumours after early promising results of therapy, the patients relapse, metastases appear, and acquired resistance to chemotherapy develops. The broad spectrum-resistance against chemotherapy is called multidrug resistance (MDR), and due to its clinical significance, studying of proteins responsible for multidrug resistance has become one of the most active research areas in biomedicine. There are several molecular mechanisms responsible for multidrug resistance. A group of filogenetically conservative plasmamembrane proteins actively extrudes different toxic compounds, xenobiotics, and also cytotoxic drugs from drug-resistant cells by using the energy of ATP. The clinically and biochemically most thoroughly characterized member of these proteins is the P-glycoprotein, which pumps hydrophobic drugs of natural origin and different chemical structure out of the cells. The recently cloned multidrug resistance associated protein (MRP) has also a broad substrate specificity, thus resembling P-glycoprotein. However, besides hydrophobic compounds, organic anions, glucuronide and glutathione conjugates are also excellent substrates of the MRP. The basic and clinically relevant properties of proteins causing multidrug resistance and the state of the art of current diagnostic approaches are summarized in this literature review. The different malignancies are characterized from the point of view of their multidrug resistance and recent clinical and biochemical data concerning therapeutic approaches for reversal of multidrug resistance are also presented.
Semmelweis OTE II., Belklinika, Budapest.
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D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018432:Drug Resistance, Multiple; D006801:Humans; D009369:Neoplasms / Q000145:classification / Q000188:drug therapy*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1