ABC Transporters and Multidrug Resistance

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.

PREFACE ix

CONTRIBUTORS xi

INTRODUCTION: WHAT IS MULTIDRUG RESISTANCE? 1
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 15

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

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

3 ABCG2: A new challenge in cancer drug resistance 83
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 119

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

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

PART III ABC PROTEINS AND PATHOGENIC MICROORGANISMS 177

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

7 ABC proteins involved in protozoan parasite resistance 195
Bruno Pradines

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 241
Hamid Morjani and Claudie Madoulet

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

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

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

12 Multidrug resistance reversal in solid tumors 349
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 363

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

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

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

PERSPECTIVES 437

INDEX 441