Genomics and Pharmacogenomics in Anticancer Drug Development and Clinical Response

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.

List of contents

Genomic Experimental Approaches in Oncology.- Toward the Realization of the Promise of Microarrays in Oncology.- Cell-Based Models to Identify Genetic Variants Contributing to Anticancer Drug Response.- Proteomic Analysis in Cancer Patients.- MicroRNAs and Discovery of New Targets.- Pharmacogenomics of the National Cancer Institute's 60-Tumor Cell Panel.- Use of Single-Nucleotide Polymorphism Array for Tumor Aberrations in Gene Copy Numbers.- Pharmacogenomics of Toxicity and Response of Chemotherapy.- Concordance Between Tumor and Germline DNA.- Epidermal Growth Factor Receptor Mutations and Sensitivity to Selective Kinase Inhibitors in Human Lung Cancer.- BCR-ABL Mutations and Imatinib Resistance in Chronic Myeloid Leukemia Patients.- Role of Thymidylate Synthase Gene Variations in Colorectal Cancer Patients.- Thiopurines in the Treatment of Childhood Acute Lymphoblastic Leukemia and Genetic Variants of the Thiopurine S-Methyltransferase Gene.- Impact of Polymorphisms on the Clinical Outcomes of Monoclonal Antibody Therapy Against Hematologic Malignancies.- DNA Repair and Mitotic Checkpoint Genes as Potential Predictors of Chemotherapy Response in Non-Small-Cell Lung Cancer.- Dihydropyrimidine Dehydrogenase (Dpyd) Gene Polymorphism: Portrait of a Serial Killer.- Impact of UDP-Glucuronosyltransferase 1A Haplotypes on Irinotecan Treatment.- Microarray Profiling in Breast Cancer Patients.- Role of the Folate-Pathway and the Thymidylate Synthase Genes in Pediatric Acute Lymphoblastic Leukemia Treatment Response.- Pharmacogenomics in Clinical Drug Development in Oncology.- Pharmacogenomics in Drug Development: A Pharmaceutical Industry Perspective.- Identification of Pharmacogenomic Biomarker Classifiers in Cancer Drug Development.- Toxicogenomics Application to OncologyDrug Development.- Strategies to Identify Pharmacogenomic Biomarkers: Candidate Gene, Pathway-Based, and Genome-Wide Approaches.

Summary

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.

Additional text

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)

Report

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)

Product details

• Assisted by: Federic Innocenti (Editor), Federico Innocenti (Editor)
• Publisher: Springer, Berlin
• Languages: English
• Product format: Paperback / Softback
• Released: 18.11.2010
• EAN: 9781617376948
• ISBN: 978-1-61737-694-8
• No. of pages: 378
• Weight: 966 g
• Illustrations: XIV, 378 p. 53 illus., 3 illus. in color.
• Series: Cancer Drug Discovery and Development; Cancer Drug Discovery and Development
• Subjects: Natural sciences, medicine, IT, technology > Medicine > Clinical medicine; C, Pharmacology, Human Genetics, Biomedical and Life Sciences, Cancer Research, Medical Genetics, Biomedical Research, Pharmacology/Toxicology