Genomics and Pharmacogenomics in Anticancer Drug Development and Clinical Response

1. Front Matter

   Pages i-xiv

   PDF

2. Genomic Experimental Approaches in Oncology

   1. Front Matter

      Pages 1-1

      PDF

   2. Toward the Realization of the Promise of Microarrays in Oncology

      • Natalie Stickle, Neil Winegarden

      Pages 3-18

   3. Cell-Based Models to Identify Genetic Variants Contributing to Anticancer Drug Response

      • M. Eileen Dolan, Howard McLeod

      Pages 19-31

   4. Proteomic Analysis in Cancer Patients

      • Yasuhiro Kuramitsu, Kazuyuki Nakamura

      Pages 33-45

   5. MicroRNAs and Discovery of New Targets

      • Soken Tsuchiya, Yasushi Okuno, Gozoh Tsujimoto

      Pages 47-56

   6. Pharmacogenomics of the National Cancer Institute’s 60-Tumor Cell Panel

      • Anders Wallqvist, Ruili Huang, David G. Covell

      Pages 57-74

   7. Use of Single-Nucleotide Polymorphism Array for Tumor Aberrations in Gene Copy Numbers

      • Kwong-Kwok Wong

      Pages 75-88

3. Pharmacogenomics of Toxicity and Response of Chemotherapy

   1. Front Matter

      Pages 90-90

      PDF

   2. Concordance Between Tumor and Germline DNA

      • Sharon Marsh

      Pages 91-101

   3. Epidermal Growth Factor Receptor Mutations and Sensitivity to Selective Kinase Inhibitors in Human Lung Cancer

      • Anurag Singh, Sreenath V. Sharma, Jeffrey Settleman

      Pages 103-126

   4. BCR-ABL Mutations and Imatinib Resistance in Chronic Myeloid Leukemia Patients

      • Mark R. Litzow

      Pages 127-150

   5. Role of Thymidylate Synthase Gene Variations in Colorectal Cancer Patients

      • Georg Lurje, Heinz-Josef Lenz

      Pages 151-172

   6. Thiopurines in the Treatment of Childhood Acute Lymphoblastic Leukemia and Genetic Variants of the Thiopurine S-Methyltransferase Gene

      • Martin Stanulla, Elke Schaeffeler, Matthias Schwab

      Pages 173-201

   7. Impact of Polymorphisms on the Clinical Outcomes of Monoclonal Antibody Therapy Against Hematologic Malignancies

      • Dong Hwan Kim

      Pages 203-229

   8. DNA Repair and Mitotic Checkpoint Genes as Potential Predictors of Chemotherapy Response in Non-Small-Cell Lung Cancer

      • Rafael Rosell, Miquel Taron, Mariacarmela Santarpia, Fernanda Salazar, Jose Luis Ramirez, Miguel Angel Molina

      Pages 231-247

   9. Dihydropyrimidine Dehydrogenase (Dpyd) Gene Polymorphism: Portrait of a Serial Killer

      • Joseph Ciccolini, Cédric Mercier, Gérard Milano

      Pages 249-265

   10. Impact of UDP-Glucuronosyltransferase 1A Haplotypes on Irinotecan Treatment

       • Kimie Sai, Hironobu Minami, Yoshiro Saito, Jun-ichi Sawada

       Pages 267-286

   11. Microarray Profiling in Breast Cancer Patients

       • Yong Qian, Xianglin Shi, Vincent Castranova, Nancy L. Guo

       Pages 287-298

   12. Role of the Folate-Pathway and the Thymidylate Synthase Genes in Pediatric Acute Lymphoblastic Leukemia Treatment Response

       • Lea Cunningham, Richard Aplenc

       Pages 299-310

Genomics and Pharmacogenomics in Anticancer Drug Development and Clinical Response provides the most comprehensive body of knowledge available on the role of genetic and genomic variation in the individualization of drug therapies in cancer patients. As a consequence of the intrinsic chromosomal and genetic instability of the tumor genome, it is generally believed that tailoring of chemotherapy in cancer - tients might be achieved by molecular analysis of patient tumor DNA. In addition, to reduce the toxicity risk of patients, the tumor DNA information should be in- grated with the available data on polymorphic drug-metabolizing enzyme and tra- porter genes mediating the exposure of patients to active drugs and/or their active metabolites. The chapters of this book clearly show how DNA information from both the host (germline) and the tumor should be taken into account for rational selection of drug therapies in cancer patients, an aspect that received little attention, despite its importance. The availability of new molecular approaches to the selection of drug therapy is an emerging need, because the traditional approach based on the evaluation of patient and tumor characteristics is clearly far from optimal. Many treated patients do not experience signi?cant bene?ts from the treatment, while they often experience moderate to severe toxicities. In addition, the development and clinical use of novel molecularly targeted agents (alone or in combination with classical cytotoxic therapy) requires the und- standing of the molecular features of the tumors and the identi?cation of tumor markers of response.

• DNA
• Drogen
• MicroRNAs
• Microarrays
• Oncology drug development
• Pharmacogenomics
• Single Nucleotide Polymorphism
• Toxicogenomics
• anticancer drug response
• genes
• oncology
• proteomic analysis
• tumor DNA

From the reviews:

"The chapters of this book, written by outstanding scientists in the field of cancer pharmacogenomics, clearly show how DNA information from both the host and the tumor should be taken into account for rational selection of drug therapies in cancer patients. … the book provides a comprehensive and in-depth view of the field of cancer pharmacogenomics. The book is informative for clinicians, for people involved in development of cancer therapeutics on industrial level, and any scientists who are interested in cancer biology." (C. Altaner, Neoplasma, June, 2009)

"The chapters of this book, written by outstanding scientists in the field of cancer pharmacogenomics … . the book provides a comprehensive and in-depth view of the field of cancer pharmacogenomics. The book is informative for clinicians, for people involved in development of cancer therapeutics on industrial level, and any scientists who are interested in cancer biology." (C. Altaner, Neoplasma, April, 2009)

• Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, USA

  Federico Innocenti

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