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.
INTRODUCTION: WHAT IS MULTIDRUG RESISTANCE? 1Jonathan 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? 17Fabienne Grandjean–Forestier, Christophe Stenger, Jacques Robert, Mireille Verdier, and Marie–Hélène Ratinaud
2 Multidrug resistance–associated protein (MRP/ABCC proteins) 47Mylène Honorat, Charles Dumontet, and Lea Payen
3 ABCG2: A new challenge in cancer drug resistance 83Orsolya 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 121Ollivier Legrand, Ruo–Ping Tang, and Jean–Pierre Marie
5 ABC proteins and oncology: Expression, detection, and implication of ABC proteins in solid tumors 143Jean 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 179Serge Michalet and Marie–Geneviève Dijoux–Franca
7 ABC proteins involved in protozoan parasite resistance 195Bruno 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 241Hamid Morjani and Claudie Madoulet
9 Reversal agents of multidrug resistance mediated by multidrug resistance–associated proteins (MRPs) 261Ahcène Boumendjel, Anne Florin, and Jean Boutonnat
10 Reversal agents for breast cancer resistance protein (BCRP)–mediated multidrug resistance 289Jean Boutonnat, Anne Florin, and Ahcène Boumendjel
11 Strategies to overcome drug resistance in acute and chronic leukemias 315Eric Solary, Vincent Ribrag, and Stéphane de Botton
12 Multidrug resistance reversal in solid tumors 349Tatiana 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 365Jean–Michel Scherrmann
14 The role of ABC transporters at the intestinal barrier 385Roos L. Oostendorp, Jos H. Beijnen, and Jan H.M. Schellens
15 Genetic polymorphisms in ABC transporters 411Leslie W. Chinn and Deanna L. Kroetz