ABC Transporters and Multidrug Resistance / Edition 1

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A comprehensive review of the most current scientific research on ABC transporters and multidrug resistance

ATP-binding cassette transporter genes (ABC transporters) are known to play a crucial role in the development of multidrug resistance (MDR). MDR is the ability of pathologic cells, such as tumors, to withstand chemicals designed to target and destroy such cells. In MDR, patients who are on medication eventually develop resistance to not only the drug they are taking, but to several different types of drugs.

ABC Transporters and Multidrug Resistance offers an essential resource for pharmaceutical researchers who are working to discover drugs to counteract multidrug resistance in diseases such as cancer. In one comprehensive volume, this book contains a collection of the most current knowledge on the involvement of ABC transporters in drug transport and resistance.

This comprehensive volume provides an overview on the description of the structure, the genome, normal tissue expression, physiological aspect, and mechanism of action of the ABC protein. The expert contributors explore the expression, detection, and implications of ABC proteins in hematological malignancies and solid tumors and ABC proteins and pathogenic microorganisms. This volume also explains MDR modulation through inhibition of ABC transporters and the design of inhibitors and mechanism of action. In addition, the book offers essential information on the biological and clinical aspect of multidrug resistance.

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Editorial Reviews

From the Publisher
"The book is both interesting for both novice and experienced researches in the field." (ChemMedChem, July 2010)
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Product Details

Meet the Author

Ahcéne Boumendjel is Professor of Medicinal Chemistry at the University of Grenoble School of Pharmacy, France.

Jean Boutonnat is an Assistant Professor and Hospital Practitioner at the Grenoble Medical School and Université Joseph Fourier of Grenoble, France.

Jacques Robert is Professor and Head of the Laboratory of Pharmacology of Anticancer Agents at Institut Bergonié and Université Victor Segalen Bordeaux 2, France.

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Table of Contents

Preface ix

Contributors xi

Introduction: What is Multidrug Resistance? Jonathan A. Sheps Victor Ling 1

Part I ABC Proteins: An Overview and Description of the Structure, Genome, Normal Tissue Expression, Physiological Aspect, and Mechanism of Action 15

1 The P-glycoprotein 170: Just a multidrug resistance protein or a protean molecule? Fabienne Grandjean-Forestier Christophe Stenger Jacques Robert Mireille Verdier Marie-Hélène Ratinaud 17

2 Multidrug resistance-associated protein (MRP/ABCC proteins) Myléne Honorat Charles Dumontet Lea Payen 47

3 ABCG2: A new challenge in cancer drug resistance Orsolya Polgar Robert W. Robey Kin Wah To John Deeken Patricia A. Fetsch Susan E. Bates 83

Part II ABC Proteins and Oncology: Expression, Detection, and Implication of ABC Proteins in Hematological Malignancies and Solid Tumors 119

4 Expression, detection, and implication of ABC proteins in acute myeloblastic leukemia Ollivier Legrand Ruo-Ping Tang Jean-Pierre Marie 121

5 ABC proteins and oncology: Expression, detection, and implication of ABC proteins in solid tumors Jean Fran&ccidle;ois Bernaudin Anne Fajac Jocelyne Fleury-Feith Khaldoun Kerrou Roger Lacave 143

Part III ABC Proteins and Pathogenic Microorganisms 177

6 ABC transporters and resistance to antibiotics Serge Michalet Marie-Geneviève Dijoux-Franca 179

7 ABC proteins involved in protozoan parasite resistance Bruno Pradines 195

Part IV Multidrug Resistance (MDR) Modulation Through Inhibition of ABC Transporters: Design of Inhibitors and Mechanism of Action 239

8 Reversal agents for P-glycoprotein-mediated multidrug resistance Hamid Morjani Claudie Madoulet241

9 Reversal agents of multidrug resistance mediated by multidrug resistance-associated proteins (MRPs) Ahcène Boumendjel Anne Florin Jean Boutonnat 261

10 Reversal agents for breast cancer resistance protein (BCRP)-mediated multidrug resistance Jean Boutonnat Anne Florin Ahcène Boumendjel 289

11 Strategies to overcome drug resistance in acute and chronic lenkemias Eric Solary Vincent Ribrag Stéphane de Botton 315

12 Multidrug resistance reversal in solid tumors Tatiana Bogush Jacques Robert 349

Part V Biological and Clinical Aspects of Multidrug Resistance: The Role of the Transporters at the Main Protection Barriers (ABCB1, ABCC1, ABCC2, ABCG2) on the Bioavailability of Many Types of Drugs and Medications 363

13 ABC superfamily transporters at the human blood-brain barrier Jean-Michel Schermann 365

14 The role of ABC transporters at the intestinal barrier Roos L. Oostendorp Jos H. Beijnen Jan H.M. Schellens 385

15 Genetic polymorphisms in ABC transporters Leslie W. Chinn Deanna L. Krotez 411

Perspectives 437

Index 441

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