Multi-Drug Resistance in Cancer

Chemotherapy is one of the major treatment options for cancer patients; however, the efficacy of chemotherapeutic management of cancer is severely limited by multidrug resistance, in that cancer cells become simultaneously resistant to many structurally and mechanistically unrelated drugs. In the past three decades, a number of mechanisms by which cancer cells acquire multidrug resistance have been discovered. In addition, the development of agents or strategies to overcome resistance has been the subject of intense study. This book contains comprehensive and up-to-date reviews of multidrug resistance mechanisms, from over-expression of ATP-binding cassette drug transporters such as P-glycoprotein, multidrug resistance-associated proteins, and breast cancer resistance p- tein to the drug ratio-dependent antagonism and the paradigm of cancer stem cells. The book also includes strategies to overcome multidrug resistance, from the development of compounds that inhibit drug transporter function to the modulation of transporter expression. In addition, this book contains techniques for the detection and imaging of drug transporters, methods for the investigation of drug resistance in animal models, and strategies to evaluate the efficacy of resistance reversal agents. The book intends to provide a state-of-the-art collection of reviews and methods for both basic and clinician investigators who are interested in cancer multidrug resistance mechanisms and reversal strategies. Tianjin, China Jun Zhou v Contents Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix 1 Multidrug Resistance in Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Bruce C. Baguley 2 Multidrug Resistance in Oncology and Beyond: From Imaging of Drug Efflux Pumps to Cellular Drug Targets . . . . . . . . . . . . . . . . . . . . . . . . . .

1. Multidrug Resistance in Cancer Bruce C. Baguley 2. Multidrug Resistance in Oncology and Beyond: From Imaging of Drug Efflux Pumps to Cellular Drug Targets Wouter B. Nagengast, Thijs H. Oude Munnink, Eli C.F. Dijkers, Geke A.P. Hospers, Adrienne H. Brouwers, Carolien P. Schröder, Marjolijn Lub-de Hooge, and Elisabeth G.E. de Vries 3. Studying Drug Resistance Using Genetically Engineered Mouse Models for Breast Cancer Sven Rottenberg, Marina Pajic, and Jos Jonkers 4. Mechanisms of Multidrug Resistance in Cancer Jean-Pierre Gillet and Michael M. Gottesman 5. Molecular Mechanisms of Drug Resistance in Single-Step and Multi-Step Drug-Selected Cancer Cells Anna Maria Calcagno and Suresh V. Ambudkar 6. Pharmacogenetics of ATP-Binding Cassette Transporters and Clinical Implications Ingolf Cascorbi and Sierk Haenisch 7. Flow Cytometric Evaluation of Multidrug Resistance Proteins Adorjan Aszalos and Barbara J. Taylor 8. Targeted Chemotherapy in Drug Resistant Tumors and Noninvasive Imaging of P-Glycoprotein-Mediated Functional Transport in Cancer Jothilingam Sivapackiam, Seth T. Gammon, Scott E. Harpstrite, and Vijay Sharma 9. Epigenetic Regulation of Multidrug Resistance 1 Gene Expression: Profiling CpG Methylation Status Using Bisulphite Sequencing Emma K. Baker and Assam El-Osta 10. Expression and Function of P-Glycoprotein in Normal Tissues: Effect on Pharmacokinetics Frantisek Staud, Martina Ceckova, Stanislav Micuda, and Petr Pavek 11. Molecular Mechanism of ATP-Dependent Solute Transport by Multidrug Resistance-Associated Protein 1 Xiu-bao Chang 12. Impact of Breast Cancer Resistance Protein on Cancer Treatment Outcomes Douglas D. Ross and Takeo Nakanishi 13. Drug Ratio-Dependent Antagonism: A NewCategory of Multidrug Resistance and Strategies for Its Circumvention Troy O. Harasym, Barry D. Liboiron, and Lawrence D. Mayer 14. Reversing Agents for ATP-Binding Cassette Drug Transporters Chow H. Lee 15. Overcoming Multidrug Resistance in Cancer: Clinical Studies of P-Glycoprotein Inhibitors Helen M. Coley 16. Pharmacokinetic and Pharmacodynamic Implications of P-Glycoprotein Modulation Jeannie M. Padowski and Gary M. Pollack 17. Examination of CYP3A and P-Glycoprotein-Mediated Drug-Drug Interactions Using Animal Models Punit H. Marathe and A. David Rodrigues 18. Generating Inhibitors of P-Glycoprotein: Where to, Now? Emily Crowley, Christopher A. McDevitt, and Richard Callaghan 19. Immunosuppressors as Multidrug Resistance Reversal Agents Hamid Morjani and Claudie Madoulet 20. Overcoming Multidrug Resistance by RNA Interference Alexandra Stege, Andrea Krühn, and Hermann Lage 21. Circumventing Tumor Resistance to Chemotherapy by Nanotechnology Xing-Jie Liang, Chunying Chen, Yuliang Zhao, and Paul C. Wang