Multidrug resistance: focus in hematology.
The appearance of chemoresistance is the most relevant limitation of chemotherapy. It has been shown that multidrug resistance (MDR) is frequently related to the expression of a membrane glycoprotein (P-170). This protein is able to bind ATP and leads to decreased accumulation of structurally unrelated antineoplastic drugs extensively used in the management of hematological patients. The availability of monoclonal antibodies and probes allowed extensive studies both "in vitro" and "in vivo" of the protein structure and of its mechanism of action. The P 170 activity may be antagonized by drugs able to compete with chemotherapic agents for the binding or by calcium antagonists that inhibit the expulsion activity of the protein. P 170 has been found in variable percentages of several hematological malignancies such as leukemia, myelodysplastic syndromes, myeloma and lymphoma. The reported data seem to indicate that the patients carrying P 170-positive neoplastic cells should be treated with drugs that are not bound by the protein. However, the possibility of inhibiting the protein function and the recent reports suggesting the use of P 170 as a target for immunotoxins could be the basis for new therapeutic protocols.
Carulli
G
G
Servizio di Ematologia, Clinica Medica I, Università, Pisa, Italy.
Petrini
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001693:Biological Transport, Active; D004247:DNA / Q000235:genetics; D004351:Drug Resistance; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D007694:Killer Cells, Natural / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000235:genetics; D010641:Phenotype; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014700:Verapamil / Q000627:therapeutic use
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D014700:Verapamil