DNA Repair in Cancer Therapy

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 which primarily results from the front line cancer treatments; chemotherapy and radiation. This comprehensive and timely reference will focus 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. Edited by 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 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 Susan Ashwell 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 Srinivasan Madhusudan 13. The Role of DNA Damage and Repair in Neurotoxicity Caused by Cancer Therapies Michael R. Vasko 14. Future Directions Mark R. Kelley