Cytotoxic Drug Resistance Mechanisms / Edition 1

by Robert Brown, Uta Böger-Brown

Overview

There is now a range of cytotoxic drugs that have considerable clinical usefulness in producing responses in tumors and even, in a small proportion of cases, cure. However, the acquisition of drug resistance is a major clinical problem and is perhaps the main limiting factor in successful treatment of cancer. Thus, a tumor initially sensitive to chemotherapy will, in the majority of cases, eventually recur as a resistant tumor, which will then progress. Much of our understanding of drug resistance mechanisms comes from the study of tumor cell lines grown in tissue culture. We now understand many of the - lecular mechanisms that can lead to a cell acquiring resistance to antic- cer drugs; however, we still do not know which mechanism(s) are those most relevant to the problem of clinical drug resistance. Indeed, given that many of the cytotoxic anticancer drugs were discovered by random screening, it is - clear what features give a clinically useful anticancer drug a sufficient the- peutic index to be of value. The aim of Cytotoxic Drug Resistance Mechanisms is to provide pro- cols that are appropriate for examining the mechanisms of cellular resistance to anticancer cytotoxics in human tumor samples. Tumor cell lines have been enormously useful as experimental models of drug resistance mechanisms, however they have limitations and we need to address the relevance of such mechanisms in patients’ tumors. Examining drug resistance in tumors is much more problematic than in cell lines.

Product Details

ISBN-13:	9781617370939
Publisher:	Springer-Verlag New York, LLC
Publication date:	11/09/2010
Series:	Methods in Molecular Medicine , #28
Edition description:	Softcover reprint of hardcover 1st ed. 1999
Pages:	238
Product dimensions:	5.98(w) x 9.02(h) x 0.35(d)

About the Author

Brown, Robert (Univ of Glasgow); Boger-Brown, Uta (BioMedEx, Killearn, UK)

Table of Contents

Drug Resistance.- Cell Sensitivity Assays.- Cell Sensitivity Assays.- Cell Sensitivity Assays.- Analysis of Apoptosis in Tissue Sections.- Measurement of P-glycoprotein Function.- Measuring MDR-1 by Quantitative RT-PCR.- Microtiter Plate Technique for the Measurement of Glutathione in Fresh and Cryopreserved Lymphoblasts Using the Enzyme Recycling Method.- Measurement of Reduced Glutathione Using High-Pressure Liquid Chromatography.- Topoisomerase I and II Activity Assays.- 5-Fluorouracil Metabolizing Enzymes.- Measuring DNA Adducts by Immunoassay (ELISA).- Measuring Drug-DNA Adducts in Individual Cells.- Measurement of Drug-Induced DNA Interstrand Crosslinking Using the Single-Cell Gel Electrophoresis (Comet) Assay.- PCR Analysis of Microsatellite Instability.- O 6-Alkylguanine-DNA Alkyltransferase Assay.- Analysis of the p53 Status of Tumors.- Bcl-2 Family Immunohishemistry.- Genetic Analysis of Drug Resistance by Fluorescence In Situ Hybridization.- Genetic Analysis of Drug Resistance by Reverse In Situ Hybridization.

Editorial Reviews

4 Stars! from Doody

This is a guidebook for conducting investigations on the effect of drugs on cancer cells. The purpose is to provide practical research protocols for researchers working in the field of resistance to anti-cancer agents. This book serves as a guidepost for the basic scientist, providing practical and specific protocols for the conduct of critical, technically demanding assays. In addition, it is a useful reference manual for clinical investigators, serving to provide a broad overview of specific assay types and their applicability within the context of clinical trials. All individuals involved in the field of drug development and drug resistance would benefit from this book, which is written and edited by a panel of well respected and accomplished individuals. Contained within individual chapters of this book are concise and technical overviews of assay methodologies and their relationship to underlying cancer cell biology and drug resistance. The format provides for rapid access to step-by-step protocols, followed by a pertinent discussion of both the strengths and limitations of individual approaches. This timely book will greatly benefit a wide array of individuals interested in cancer therapeutics, at both the clinical and basic science level. The editors and contributors did a good job of concisely presenting otherwise disparate methodologies in the context of a broad research field with the uniting purpose of understanding the biology underlying resistance to cancer chemotherapy. This well-chosen selection of methodologies and techniques of direct applicability to the field of drug resistance will serve as a practical way to unite a field encompassing a wide variety ofdisciplines.

Raymond Bergan

Describes methods for examining the mechanisms of cellular resistance to anticancer cytotoxics in human tumors. Review articles explain drug resistance methodology, and protocols contain detailed instructions and troubleshooting tips that allow researchers to study a variety of drug resistance mechanisms, including aspects of drug-induced cell death, drug uptake/efflux, drug metabolism, and DNA repair. Each method is designed to help identify the correlation between molecular and biochemical data and the clinical responses of the patient. Annotation c. by Book News, Inc., Portland, Or.

Booknews

Reviewer: Raymond C. Bergan, MD (Northwestern University Feinberg School of Medicine)
Description: This is a guidebook for conducting investigations on the effect of drugs on cancer cells.
Purpose: The purpose is to provide practical research protocols for researchers working in the field of resistance to anti-cancer agents.
Audience: This book serves as a guidepost for the basic scientist, providing practical and specific protocols for the conduct of critical, technically demanding assays. In addition, it is a useful reference manual for clinical investigators, serving to provide a broad overview of specific assay types and their applicability within the context of clinical trials. All individuals involved in the field of drug development and drug resistance would benefit from this book, which is written and edited by a panel of well respected and accomplished individuals.
Features: Contained within individual chapters of this book are concise and technical overviews of assay methodologies and their relationship to underlying cancer cell biology and drug resistance. The format provides for rapid access to step-by-step protocols, followed by a pertinent discussion of both the strengths and limitations of individual approaches.
Assessment: This timely book will greatly benefit a wide array of individuals interested in cancer therapeutics, at both the clinical and basic science level. The editors and contributors did a good job of concisely presenting otherwise disparate methodologies in the context of a broad research field with the uniting purpose of understanding the biology underlying resistance to cancer chemotherapy. This well-chosen selection of methodologies and techniques of direct applicability to the field of drug resistance will serve as a practical way to unite a field encompassing a wide variety of disciplines.

Doody's Review Service

"This timely book will greatly benefit a wide array of individuals interested in cancer therapeutics, at both the clinical and basic science level. The editors and contributors did a good job of concisely presenting otherwise disparate methodologies in the context of a broad research field with the uniting purpose of understanding the biology underlying resistance to cancer chemotherapy. "-Doody's Health Sciences Book Review Journal

"...the editors have managed to successfully compile a brief review of cytotoxic drug resistance mechanisms and an extensive manual of prools for laboratory experimentation in this extremely important area of research. It is clear that any laboratory scientist in this field must be aware of the difficulty of translation to the clinic of anti-drug resistance lead compounds, and should keep a copy of this book within reach. Congratulations to the editors for assembling an important mix of laboratory and clinical scientists to create this volume."-The Quarterly Review of Biology

"This book provides a comprehensive guide to a range of methods to a diverse range of drug resistance mechanisms including: Multidrug resistance (P-glycoprotein and MDR-1 gene analysis); cell sensitivity (clonogenic and MTT assays); Apoptosis (TUNEL, p 53 and Bcl-2); Glutathione-associated resistance (enzyme based glutathione assay and a HPLC method for reduced glutathione); DNA repair defects and damage (topoisomerase activity assays and DNA adduct measurements); 5-Fluorouracil metabolizing enzymes; Genetic analysis including microsatellite instability and fluorescence in situ hybridization....The methods are clearly described with each chapter consisting of an introduction and well described materials and methods sections. An extremely useful addition to most chapters was the "Notes" section where the respective authors suggest very useful hints, problem solving approaches and advice on the interpretation of results....the book is well written and useful addition to any laboratory investigating drug resistance in either clinical samples or tumor cell lines."-Cancer Forum

"...a useful collection of prools that can be used in the oncology laboratory for studies on drug resistance and molecular pharmacology....It should find its place on the library shelves of many laboratories of oncology."- Annals of Oncology

From the Publisher