Cancer therapeutics include an ever-increasing array of tools at the disposal of clinicians in their treatment of this disease. However, cancer is a tough opponent in this battle, and current treatments, which typically include radiotherapy, chemotherapy and surgery, are not often enough to rid the patient of his or her cancer. Cancer cells can become resistant to the treatments directed at them, and overcoming this drug resistance is an important research focus. Additionally, increasing discussion and research is centering on targeted and individualized therapy. While a number of approaches have undergone intensive and close scrutiny as potential approaches to treat and kill cancer (signaling pathways, multidrug resistance, cell cycle checkpoints, anti-angiogenesis, etc.), other approaches have focused on blocking the ability of a cancer cell to recognize and repair the damaged DNA that primarily results from the front-line cancer treatments; chemotherapy and radiation.
This comprehensive and timely reference focuses on the translational and clinical use of DNA repair as a target area for the development of diagnostic biomarkers and the enhancement of cancer treatment.
Academic, medical, and pharmaceutical researchers in cancer biology, cancer drug development, and cancer prevention/therapeutics, including cell biologists, biological chemists, geneticists, pharmacologists, oncologists, and radiation oncologists.
"This volume, orchestrated by Mark R. Kelley from Indiana University, offers 14 chapters by acknowledged experts that address the particular relationship between DNA repair and cancer. The content of the book is considerably broadened and enhanced by addressing topics such as the possible use of alterations in DNA as predictive biomarkers and the role of DNA damage and its repair in neurotoxicity associated with cancer therapy. Kelley appropriately concludes the volume with a thoughtful exploration of future directions in the use of inhibitors of the DNA damage response."
-- Errol C. Friedberg, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA
"DNA Repair in Cancer Therapy is an excellent primer for the cancer researcher interested in learning about the role of DNA repair in malignancy. Its chapters are accessible to the generalist yet offer a depth of discussion which is both comprehensive and detailed. This book should serve as an excellent entry to a complex field and a useful resource to all those seeking an in-depth review of this rapidly evolving area of drug discovery and development."
--Homer L. Pearce, Ph.D., Eli Lilly and Co. (retired)
"DNA Repair in Cancer Therapy provides the reader with a primer-level introduction to the six major DNA repair pathways, their interrelationships, their connectivity and regulation by other cellular operational systems, as well as their impact in shaping the development of effective cancer therapies. Chapters are well-written, detailed and up-to-date. The challenges that face new anticancer drug development based on DNA repair targets are clearly laid out and succinctly discussed with an emphasis on particular directions that are likely to result in success. The enormous complexities that have to be considered for this undertaking are placed into an understandable context and dealt with in a logical and clear fashion. The landscape of opportunity in this area is vast and challenging but has the potential to produce results that will make a real difference in patient responses to radio- and chemotherapy. This book should be of great interest and value to a variety of readers, including basic, translational and clinical scientists as well as individuals in the pharmaceutical and technology development industries."
-- Paul W. Doetsch, Ph.D., Professor of Biochemistry, Radiation Oncology, and Hematology & Medical Oncology, Distinguished Chair of Cancer Research, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA
Table of Contents
1.Introduction and Overview of Current Targets: Bench to Clinic
Mark R. Kelley
2.MGMT a Critical DNA Repair Gene Target for Chemotherapy Resistance
Stanton L. Gerson and Lili Liu
3.Blockade of Base Excision Repair: Inhibitionof Small Lesions Results in Big Consequences to Cancer Cells
Melissa Fishel and Carlo Vascotto
4.PARP Inhibitors - Scientific Rationale and Clinical Development for Cancer
Ruth Plummer, Nicola J. Curtin and Yvette Drew
5.Inhibiting Selective DNA Polymerases for Therapeutic Intervention
Anthony J. Berdis
6.Targeting the Nucleotide Excision Repair Pathway for Therapeutic Applications
John Turchi and Stephan M. Patrick
7.Homologous Recombination and ATM/ATR Targets
Henning Willers, Lee Zou and Heike N. Pfaffle
8.DNA Double Strand Break Repair by Nonhomologous End Joining and its Clinical Relevance
Michael Weinfeld and Susan Lees-Miller
9.Defective MMR-c-Abl-p73-GADD45alpha Expression in Cancer Chemoresistance
David Boothman and Long Shan Li
10.DNA Repair Signaling Targets
11.Redox Regulation of DNA Repair and Therapeutic
Millie M. Georgiadis
12.Personalized Cancer Medicine: DNA Repair Alterations is a Promising Predictive Marker in Cancer
13.The Role of DNA Damage and Repair in Neurotoxicity Caused by Cancer Therapies
Michael R. Vasko
Mark R. Kelley
Mark R. Kelley, PhD, Betty and Earl Herr Chair in Pediatric Oncology Research; Associate Director, Herman B. Wells Center for Pediatric Research; Associate Director for Basic Science Research, Simon Cancer Center, Indiana University School of Medicine; Professor, Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, USA