Radiosensitizers and Radiochemotherapy in the Treatment of Cancer: 1st Edition (Hardback) book cover

Radiosensitizers and Radiochemotherapy in the Treatment of Cancer

1st Edition

By Shirley Lehnert

CRC Press

548 pages | 4 Color Illus. | 140 B/W Illus.

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pub: 2014-12-08
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Description

Radiosensitizers and Radiochemotherapy in the Treatment of Cancer catalogs and describes the mechanism of action for entities characterized as radiosensitizers. Developments in the biological and physical sciences have introduced new radiosensitizers and defined novel targets for radiosensitization. As a result, a book about radiosensitization must now address a huge range of topics, covering everything from molecular oxygen and high Z elements to monoclonal antibodies and complex phytochemicals.

At the molecular level, the understanding of the molecular consequences of DNA damage and the DNA damage response have informed the development of targeted radiosensitizers and shed light on the mode of action of radiochemotherapy protocols of known clinical efficacy.

In this book the mechanisms of action at the molecular and cellular level are described for documented radiosensitizers including, where applicable, a brief history of their clinical use and most recent clinical results. In addition, the clinical context is addressed including the importance of factors such as dose and dose rate, normal tissue toxicity, and drug delivery. Intuitively organized by topic and application, the book includes extensive illustrations, end-of-chapter summaries, and a wealth of references.

Reviews

"This book is intended for both graduate students and seasoned researchers seeking a detailed review covering the therapeutic benefits of a combination of radiotherapy and drugs that alter the metabolism of cancer cells and their response to radiation. The summary at the end of each chapter targets the important points and directs the reader to the sections that are most relevant to him. Although preclinical studies are widely documented, the author took care to establish the links with clinical trials to appreciate the real impact of the various combinations of radio- and chemotherapy."

—Benoit Paquette, Professor and Head of the Department of Nuclear Medicine and Radiobiology, University of Sherbrooke

"This book is a great contribution to the field of radiation biology, examining the mechanisms of action, clinical uses, and targeting of radiation response modifiers, both radioprotectors and radiosensitizers. The depth and breadth of information covered in this text is exceptional and will be useful to oncologists, radiation oncologists, radiation biologists, medical physicists, and other radiation workers who seek to use radiation response modifiers in association with cancer therapy. This book will be useful in the clinical setting as well as in graduate school classrooms around the world."

—Gayle E. Woloschak, Department of Radiation Oncology, Northwestern University

Table of Contents

Radiosensitization and Chemoradiation

A Brief History of Chemoradiation

Definitions of Radiosensitization

What This Book Is About

Summary

References

Radiosensitization by Oxygen and Nitric Oxide

Radiosensitization by Oxygen: The Oxygen Fixation Hypothesis

Nitric Oxide: A Versatile Small Molecule

Summary

References

Radioenhancement by Targeting Cellular Redox Pathways and/or by Incorporation of High-Z Materials into the Target

Introduction

Dose Enhancement by Compounds with High Atomic Number

Targeting Cellular Redox Pathways

Radiosensitization by Targeting the GSH/GSSG System

Summary

References

Radiosensitization by Halogenated Pyrimidines

Halogenated Pyrimidines

Mechanisms of Radiosensitization

Clinical Results

Summary

References

Radiosensitization by Antimetabolites

Antimetabolites

Antimetabolites: Mode of Action

Inhibitors of Thymidy late Synthase: 5-FU and FDURD

Inhibitors of Ribonucleotide Reductase

DNA Polymerase Inhibitors/Substrates

New Generation Antimetabolites

Summary

References

Radiosensitization by Platinum Drugs and Alkylating Agents

The Platinum Drugs

Alkylating Agents

Summary

References

Topoisomerase Inhibitors and Microtubule-Targeting Agents

Radiosensitization by Drugs Targeting DNA Topology and the Mitotic Spindle

Topoisomerases

Radiosensitization by Targeting Microtubules

Summary

References

Targeting the DNA Damage Response: ATM, p53, Checkpoints, and the Proteasome

The DNA Damage Response

ATM Kinase

p53 in the DNA Damage Response

Targeting Cell Cycle Checkpoint Proteins: CHK1 and CHK2

Protein Degradation by the Ubiquitin–Proteasome System

Summary

References

Radiosensitization by Inhibition of DNA Repair

Overview of DNA Repair in Mammalian Cells

DNA Double-Strand Break Repair: Nonhomologous End-Joining

DNA Double-Strand Break Repair by Homologous Recombination

Radiosensitization by Inhibitors of Poly(ADP-Ribose) Polymerase

Inhibitors of Histone Deacetylase: Targeting Chromatin Modification by Epigenetic Regulation of Gene Expression

Summary

References

Targeting Growth Factor Receptors for Radiosensitization

Epidermal Growth Factor Family Receptors

ErbB2 (HER2)

Insulin-Like Growth Factor 1 Receptor

Summary

References

Targeting Signaling Molecules for Radiosensitization

Ras

Cytoplasmic Signaling Downstream from Ras

Targeting Hsp90

Summary

References

Radiosensitization by Targeting the Tumor Microenvironment

The Tumor Microenvironment

Tumor Vasculature and Angiogenesis

Tumor Characteristics Exploitable for Radiosensitization: Hypoxia

Vascular Targeted Therapies

Antivascular Therapy

Targeting HIF-1

Summary

References

Phytochemicals: Chemopreventive, Radiosensitizing, Radioprotective

Mechanism of Interaction Between Phytochemicals and Proteins

Intracellular Systems and Constituent Proteins Directly Targeted by Curcumin and Other Radiosnsitizing Phytochemicals

Targeting Proinflammatory Signaling Pathways for Tumor Radiosensitization

Phytochemicals that Have Been Shown to Act as Radiosensitizers

Radioprotection by Phytochemicals: Targeting the Proinflammatory Response to Reduce the Side Effects of Radiation

Clinical Applications of Phytochemicals

Summary

References

Delivery Methods for Radioenhancing Drugs

Delivery of Radiosensitizing Drugs

Intratumoral Sustained Drug Release Devices

Summary

References

About the Author

Shirley Lehnert is currently a professor in the Department of Oncology at McGill University in Montreal, Quebec, Canada. She graduated from London University in the UK with a PhD in biophysics. Dr. Lehnert did postdoctoral work at the University of Rochester. She conducted research in radiobiology and biophysics first at Sloane Kettering Institute and then at the Radiological Research Laboratory of Columbia University in New York. Dr. Lehnert has published extensively in the fields of radiation biology, tumor biology, and drug delivery.

About the Series

Series in Medical Physics and Biomedical Engineering

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Subject Categories

BISAC Subject Codes/Headings:
MED062000
MEDICAL / Oncology
SCI013000
SCIENCE / Chemistry / General
SCI055000
SCIENCE / Physics