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ABC Transporters and Cancer

1st Edition - January 27, 2015

Editors: Toshihisa Ishikawa, John Schuetz

Hardback ISBN:

9 7 8 - 0 - 1 2 - 8 0 1 2 5 1 - 2

eBook ISBN:

9 7 8 - 0 - 1 2 - 8 0 1 3 6 1 - 8

ABC Transporters and Cancer provides invaluable information on the exciting and fast-moving field of cancer research. Here, outstanding and original reviews are presented on a… Read more

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ABC Transporters and Cancer

provides invaluable information on the exciting and fast-moving field of cancer research. Here, outstanding and original reviews are presented on a variety of topics. This volume covers ABC transporters and cancer, and is suitable for researchers and students alike.

Dedication
Preface
Chapter one: Apical ABC Transporters and Cancer Chemotherapeutic Drug Disposition
- Abstract
- 1 Introduction to Apical ABC Transporters
- 2 Impact of Apical ABC Transporters on Intestinal Absorption of Oral Chemotherapeutic Drugs
- 3 Impact of Apical ABC Transporters on Brain Disposition of Oral Chemotherapeutic Drugs
- 4 Concluding Remarks
Chapter Two: Regulation of ABC Transporters Blood–Brain Barrier: The Good, the Bad, and the Ugly
- Abstract
- 1 Introduction
- 2 Blood–Brain Barriers
- 3 ABC Transporters at the Blood–Brain Barrier
- 4 The Bad and the Ugly: Mechanisms that Increase Transporter Expression and Reduce Drug Delivery to the CNS
- 5 The Good: Mechanisms that Reduce Transporter Activity/Expression and Have the Potential to Improve Drug Delivery to the CNS
- 6 Perspectives: Where the Field is Headed
Chapter Three: Molecular Basis of the Polyspecificity of P-Glycoprotein (ABCB1): Recent Biochemical and Structural Studies
- Abstract
- 1 Introduction
- 2 Molecular Basis of Polyspecificity
- 3 Molecular Modeling Studies
- 4 Conclusions and Perspectives
- Acknowledgments
Chapter Four: Lipid Regulation of the ABCB1 and ABCG2 Multidrug Transporters
- Abstract
- 1 Introduction—The Complex Interactions of Lipids and ABC Multidrug Transporters
- 2 Effects of Lipids on the Function of ABCB1 and ABCG2
- 3 Effects of Lipids on the Expression of ABCB1 and ABCG2: Regulation by Nuclear Receptors
- 4 Experimental Strategies to Define the Lipid-Interacting Regions of the ABCB1 and ABCG2 Proteins
- 5 In Silico Modeling of the Lipid Interactions of ABCB1 and ABCG2
- 6 Conclusions
Chapter Five: ABC Transporters and Neuroblastoma
- Abstract
- 1 Introduction
- 2 Current Therapies for Neuroblastoma
- 3 MYCN
- 4 MYCN and ABC Transporters
- 5 Non-Drug Transport Roles of ABCC1, ABCC3, and ABCC4 in Cancer Biology
- 6 Development of Therapeutic ABCC1 and ABCC4 Inhibitors
- 7 Considerations for Targeting ABCC1 and ABCC4 in Cancer
- 8 Conclusions
Chapter Six: Leukemia and ABC Transporters
- Abstract
- 1 Hematopoiesis and Leukemia
- 2 ABC Transporters That Export Regulatory Molecules
- 3 Kinases Impact Transporter Location and Function
- 4 Future Perspective
- Acknowledgments
Chapter Seven: Critical Role of ABCG2 in ALA-Photodynamic Diagnosis and Therapy of Human Brain Tumor
- Abstract
- 1 Introduction
- 2 Biosynthesis and Transport of Porphyrins
- 3 Enforced Biosynthesis of Protoporphyrin IX in Cancer Cells by ALA Administration
- 4 PDD and Fluorescence-Guided Microsurgery
- 5 Oxidative Stress-Mediated Gene Expression in PDT
- 6 Role of ABCG2 in PDT
- 7 Mechanism of ABCG2 Inhibition by Gefitinib
- 8 The Effect of Gefitinib on ALA-PDT in Brain Tumor U87MG Cells In Vitro
- 9 The Effect of Gefitinib on ALA-PDT in Xenograft Model
- 10 Concluding Remarks
- Acknowledgments
Chapter Eight: Role of ABC Transporters in Fluoropyrimidine-Based Chemotherapy Response
- Abstract
- 1 Introduction: The Use of Fluoropyrimidines in Cancer Chemotherapy
- 2 Overview of Transporters Involved in Cellular Uptake and Efflux of Fluoropyrimidines and Their Metabolites
- 3 Cell-Based Evidence for the Role of ABC Transporters in 5-FU Pathways
- 4 Association of ABC Transporter Expression with Resistance in Clinical Specimens
- 5 Genotype–Phenotype Correlations of ABC Transporters and Fluoropyrimidine-Based Therapy Response
- Acknowledgments
Index

Toshihisa Ishikawa

Dr. Toshihisa Ishikawa obtained the Ph.D. degree at the Graduate School of Science (Major: Biochemistry and Biophysics), Hokkaido University Japan in 1982. In the same year, he received a scholarship from the Deutscher Akademischer Austauschdienst (DAAD) and then moved to Germany. From 1982 till 1987, he was a postdoctoral fellow at the Institute of Physiological Chemistry (Prof. Helmut Sies) at the University of Düsseldorf Faculty of Medicine in Düsseldorf, West Germany. In April 1987, he returned to Japan to be appointed as Assistant Biochemist in the Department of Biochemistry, Medical School of Osaka University, Japan. In 1989, he went to Germany again to take the role of project leader in the Department of Tumor Biochemistry at the German Cancer Research Institute (DKFZ), Heidelberg. In 1991, Dr. Ishikawa left Germany for the USA, having been appointed as Assistant Professor in the Division of Pediatrics at the University of Texas M.D. Anderson Cancer Center in Houston, Texas, U.S.A. In 1993, he received the Achievement Award of the International Life Sciences Institute.

In December 1995, he was appointed Senior Scientist and Manager in the Department of Medicinal Biology at the Nagoya Central Research Laboratories of Pfizer, Inc., in Japan; and thereafter he became the Director of the Department of Research Technology Development at the Japanese Headquarters of Pfizer, Inc., in Tokyo, 1999. From 2000 till 2009, Dr. Ishikawa was Professor iat the Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Japan. In 2009, he moved to RIKEN Yokohama Institute to develop a rapid SNP detection method and to apply it to clinical pharmacogenomic research on human drug transporter genes. From 2012, he was also Professor (adjunct) at Yokohama City University Graduate School of Medicine, where he developed a platform of personalized medicine. In 2014, he founded NGO “Personalized Medicine & Healthcare” (President, Dr. Ishikawa). In addition Dr. Ishikawa has recently become Professor (adjunct) of Osaka Medical College, and he is directing a clinical research program of ALA-photodynamic therapy of brain tumor.

Dr. Ishikawa was a member of the International Nomenclature Committee for Human ABC Transporter Genes. He directed the NEDO project entitled “International standardization of in-vitro functional assay methods for human drug transporters” (2005 - 2008). He then served as a member of the Steering Committee of the FDA Critical Path Transporter Workshop (2008). Presently, Dr. Ishikawa is a member of the Emerging Issues Steering Committee of the ILSI Health and Environmental Sciences Institute (Washington DC, USA) and the International Transporter Consortium (ITC). As Chair, Dr. Ishikawa will organize the Gordon Research Conference on “Multi-Drug Efflux Systems” in Lucca, Italy, April 26-May 1, 2015.

Affiliations and expertise

NGO Personalized Medicine & Healthcare, Japan

John Schuetz

Affiliations and expertise

Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, USA