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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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.


"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



Radiosensitization by Oxygen and Nitric Oxide

Radiosensitization by Oxygen: The Oxygen Fixation Hypothesis

Nitric Oxide: A Versatile Small Molecule



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


Dose Enhancement by Compounds with High Atomic Number

Targeting Cellular Redox Pathways

Radiosensitization by Targeting the GSH/GSSG System



Radiosensitization by Halogenated Pyrimidines

Halogenated Pyrimidines

Mechanisms of Radiosensitization

Clinical Results



Radiosensitization by 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



Radiosensitization by Platinum Drugs and Alkylating Agents

The Platinum Drugs

Alkylating Agents



Topoisomerase Inhibitors and Microtubule-Targeting Agents

Radiosensitization by Drugs Targeting DNA Topology and the Mitotic Spindle


Radiosensitization by Targeting Microtubules



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



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



Targeting Growth Factor Receptors for Radiosensitization

Epidermal Growth Factor Family Receptors

ErbB2 (HER2)

Insulin-Like Growth Factor 1 Receptor



Targeting Signaling Molecules for Radiosensitization


Cytoplasmic Signaling Downstream from Ras

Targeting Hsp90



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



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



Delivery Methods for Radioenhancing Drugs

Delivery of Radiosensitizing Drugs

Intratumoral Sustained Drug Release Devices



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:
MEDICAL / Oncology
SCIENCE / Chemistry / General
SCIENCE / Physics