This text is an up-to-date review of current knowledge in the field of multiple drug resistance in human cancer. The literature up to the middle of 1993 is surveyed in specialist chapters written by different experts. Topics covered include the molecular genetics, cytogenetics and biochemistry of the MDR genes and P-glycoprotein; alternative transport proteins in MDR; topoisomerases I and II; cytochrome p450-enzymes and glutathione S-transferases in MDR; cellular models for MDR in solid tumours and haemopoietic tumours; immunochemical and molecular biological techniques for detection of MDR-related gene expression; and clinical and pharmacological strategies to circumvent resistance. The book brings together a combination of approaches to this serious clinical problem. This book covers a wide range of topics relating to the cellular and molecular biology, as well as clinical aspects, of the problem of multiple drug resistance. Specific mechanisms discussed in detail include P-Glycoprotein and other drug transport proteins; Topoisomerases I and II; Phase I and Phase II enzymes of xenobiotic metabolism.
Cellular models for MDR in solid tumours and in haemopoietic cells are discussed in detection of expression of MDR-related genes, and approaches to circumvent MDR.
P-glycoprotein structure and evolutionary homologies; J.M. Croop. Molecular analysis of the multidrug transporter; U.A. Germann. Molecular cytogenetics of multiple drug resistance; P.V. Schoenlein. Antibodies in the study of multiple drug resistance; Y. Heike, T. Tsuruo. Non-glycoprotein multidrug resistance in cell lines which are defective in the cellular accumulation of drug; M.S. Center. Topoisomerase I in multiple drug resistance; A. Pessina. Topoisomerase II in multiple drug resistance; G.A. Hoffmann, M.R. Mattern. Glutathione-related enzymes, glutathione and multidrug resistance; J.A. Moscow, K.H. Dixon. Pharmacologic circumvention of multidrug resistance; J.M. Ford, W.N. Hait. Multidrug resistance (MDR) genes in haematological malignancies; K. Nooter, P. Sonneveld. Human cell lines as models for multidrug resistance in solid tumours; M. Clynes, M. Heenan, K. Hall. Studies on low-level MDR cells; G. Belvedere, E. Dolfini. Differing patterns of cross-resistance resulting from exposures to specific antitumour drugs or to radiation; B.T. Hill. The use of reverse transcriptase-polymerase chain reaction (RT-PCR) to investigate specific gene expression in multidrug-resistant cells; L. O'Driscoll, C. Daly, M. Saleh, M. Clynes. Mathematical models for multidrug resistance and its reversal; S. Michelson. The biology of radioresistance: similarities, differences and interactions with drug resistance; S.N. Powell, Abraham. Kinetic resistance to anticancer agents; M.-T. Dimanche-Boitrel, C. Garrido, B. Chauffert. Cytochromes P450 and drug resistance; J. Doehmer, A.R. Goeptar, N.P.E. Vermeulen. Role of matrix metalloproteinases in invasion and metastasis: biology, diagnosis and inhibitors; S. McDonnell, B. Fingleton. Clinical significance of cellular resistance in tumours to cytotoxic chemotherapy and radiotherapy; M. Pomeroy, A.P. Moriarty.