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Molecular Mechanisms and Possibilities of Overcoming Drug Resistance in Gastrointestinal Tumors

  • Conference paper
New Perspectives in Molecular and Clinical Management of Gastrointestinal Tumors

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 142))

Abstract

Primary and aquired resistance of tumor cells to antineoplastic drugs is a major cause of the limited efficiency of chemotherapy. Gastrointestinal (GI) tumors have proven to express cytostatic drug resistance at an unsually high rate. One major reason for this is the multidrug resistant (MDR) phenotype which is often found in carcinomas of the stomach, bile duct, pancreas, liver, and colon. MDR is due to the overexpression of a membrane-bound glycoprotein, the so called P-glycoprotein. However, this is not the only resistance mechanisms of GI tumor cells, but the intracellular compartmentalization of drugs with subsequent release to the microenvironment represents an additional potent mechanism of drug resistance. This is independent of P-glycoprotein and as yet cannot be reversed. Alterations of glutathione-S-transferase (GST) and topoisomerase I and II may be involved either. Analyses of cell lines for cross resistance against a battery of cytostatic drugs suggest even more mechanisms which may contribute to the marked resistance of gastrointestinal cancer. Only a detailed investigation of all different types of drug insensitivity, if ever possible, might offer a chance to fully understand this multifactorial orchestra of events and to develop complex strategies for overcoming drug resistance.

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Authors and Affiliations

  1. Institut für Pathologie der Charité, Humboldt Universität zu Berlin, Schumannstr. 20-21, 10117, Berlin, Germany

    M. Dietel

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  1. M. Dietel
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Editors and Affiliations

  1. Fachbereich Humanmedizin, Univ.-Klinikum Benjamin Franklin, Medizinische Klinik und Poliklinik, Schwerpunkt Hämatologie und Onkologie, Freie Universität Berlin, Hindenburgdamm 30, 12200, Berlin, Germany

    Ernst-D. Kreuser

  2. Robert-Rössle Klinik am Max-Delbrück-Centrum, Humboldt-Universität, Lindenberger Weg 80, 13122, Berlin, Germany

    P. M. Schlag

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© 1996 Springer-Verlag Berlin Heidelberg

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Dietel, M. (1996). Molecular Mechanisms and Possibilities of Overcoming Drug Resistance in Gastrointestinal Tumors. In: Kreuser, ED., Schlag, P.M. (eds) New Perspectives in Molecular and Clinical Management of Gastrointestinal Tumors. Recent Results in Cancer Research, vol 142. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-80035-1_7

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  • DOI: https://doi.org/10.1007/978-3-642-80035-1_7

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-80037-5

  • Online ISBN: 978-3-642-80035-1

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