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Wiley Series in Drug Discovery and DevelopmentBinghe Wang, Series EditorABC Transporters and Multidrug ResistanceEdited byAhc+ne BoumendjelJean BoutonnatJacques RobertA comprehensive review of the most current scientific research on ABC transporters and multidrug resistanceATP-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, patie... MOREnts 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.

This book gathers present knowledge on the involvement of ABC transporters in drug transport and resistance. Bringing together updated information from an otherwise-scattered field of scientific literature, this resource helps researchers in pharmaceutical science in discovering drugs able to counteract multidrug resistance in diseases like cancer.

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.

PREFACE.

CONTRIBUTORS.

INTRODUCTION: WHAT IS MULTIDRUG RESISTANCE (Jonathan A. Sheps and Victor Ling).

PART I ABC PROTEINS: AN OVERVIEW AND DESCRIPTION OF THE STRUCTURE, GENOME, NORMAL TISSUE EXPRESSION, PHYSIOLOGICAL ASPECT, AND MECHANISM OF ACTION.

1 The P-glycoprotein 170: Just a multidrug resistance protein or a protean molecule (Fabienne Grandjean-Forestier, Christophe Stenger, Jacques Robert, Mireille Verdier, and Marie-Hélène Ratinaud).

2 Multidrug resistance-associa... MOREted protein (MRP/ABCC proteins) (Mylène Honorat, Charles Dumontet, and Lea Payen).

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

PART II ABC PROTEINS AND ONCOLOGY: EXPRESSION, DETECTION, AND IMPLICATION OF ABC PROTEINS IN HEMATOLOGICAL MALIGNANCIES AND SOLID TUMORS.

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

5 ABC proteins and oncology: Expression, detection, and implication of ABC proteins in solid tumors (Jean François Bernaudin, Anne Fajac, Jocelyne Fleury-Feith, Khaldoun Kerrou, and Roger Lacave).

PART III ABC PROTEINS AND PATHOGENIC MICROORGANISMS.

6 ABC transporters and resistance to antibiotics (Serge Michalet and Marie-Geneviève Dijoux-Franca).

7 ABC proteins involved in protozoan parasite resistance (Bruno Pradines).

PART IV MULTIDRUG RESISTANCE (MDR) MODULATION THROUGH INHIBITION OF ABC TRANSPORTERS: DESIGN OF INHIBITORS AND MECHANISM OF ACTION.

8 Reversal agents for P-glycoprotein-mediated multidrug resistance (Hamid Morjani and Claudie Madoulet).

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

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

11 Strategies to overcome drug resistance in acute and chronic leukemias (Eric Solary, Vincent Ribrag, and Stéphane de Botton).

12 Multidrug resistance reversal in solid tumors (Tatiana Bogush and Jacques Robert).

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.

13 ABC superfamily transporters at the human blood–brain barrier (Jean-Michel Scherrmann).

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

15 Genetic polymorphisms in ABC transporters (Leslie W. Chinn and Deanna L. Kroetz).

PERSPECTIVES.

INDEX.

Ahc?ne 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 Universit� Joseph Fourier of Grenoble, France.

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

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