DNA Repair in Cancer Therapy (Cancer Drug Discovery and Development)

Because of drug resistance, currently available anticancer therapies-drugs, radiotherapy, and other biological agents-have limited efficacy in treating cancer. In DNA Repair in Cancer Therapy, leading cancer researchers and oncologists comprehensively review the many recent developments in DNA repair that have potential for translational and clinical applications. The authors explain in detail the various mechanisms by which cancer cells can circumvent anticancer therapy and limit its usefulness in patients. They also review the clinical impact of such novel inhibitors of DNA repair mechanisms as methylguanine-DNA-methyltransferase. Inhibitors of such other DNA repair enzymes as PARP and DNA-PK, now under development and close to clinical trials, are also examined. Comprehensive and cutting-edge, DNA Repair in Cancer Therapy surveys-for both cancer researchers and practicing oncologists dealing with hallmark "relapse" or "drug resistance" phenomena on a daily basis-the many exciting new uses of DNA repair inhibitors, either alone or in combination with anticancer therapies. Front Matter....Pages i-xi Clinical Resistance to Alkylators....Pages 1-7 Role of Nonhomologous End-Joining and Recombinational DNA Repair in Resistance to Nitrogen Mustard and DNA Crosslinking Agents....Pages 9-29 Repair of DNA Interstrand Crosslinks Produced by Cancer Chemotherapeutic Drugs....Pages 31-49 Chemosensitization to Platinum-Based Anticancer Drugs....Pages 51-71 Regulation of DNA Repair and Apoptosis by p53 and Its Impact on Alkylating Drug Resistance of Tumor Cells....Pages 73-108 Stress-Activated Signal Transduction Pathways in DNA Damage Response....Pages 109-141 Overcoming Resistance to Alkylating Agents by Inhibitors of O 6 -Alkylguanine-DNA Alkyltransferase....Pages 143-169 Cellular Protection Against the Antitumor Drug Bleomycin....Pages 171-196 Potential Role of PARP Inhibitors in Cancer Treatment and Cell Death....Pages 197-210 Relationship Among DNA Repair Genes, Cellular Radiosensitivity, and the Response of Tumors and Normal Tissues to Radiotherapy....Pages 211-256 Strand-Break Repair and Radiation Resistance....Pages 257-272 V(D)J Recombination and DNA Double-Strand-Break Repair....Pages 273-293 Inherited Disorders of Genomic Instability and Cancer Susceptibility....Pages 295-321 Role of BRCA1 and BRCA2 in DNA Repair and Potential Impact on Therapeutics....Pages 323-337 Genetic Variations in DNA Repair....Pages 339-351 Back Matter....Pages 353-363

A comprehensive review of the recent developments in DNA repair that have potential for translational and clinical applications. The authors explain in detail the various mechanisms by which cancer cells can circumvent anticancer therapy and limits its usefulness in patients. They also review the clinical impact of such novel inhibitors of DNA repair mechanisms as methylguanine-DNA-methyltransferase. Also examined are inhibitors of other DNA repair enzymes such as PARP and DNA-PK, now under development and close to clinical trials. The book captures-for both cancer researchers and practicing oncologists dealing with hallmark "relapse" or "drug resistance" phenomena on a daily basis-the many exciting new uses of DNA repair inhibitors, either alone or in combination with anticancer therapies.

This volume is concerned with the hallmark "relapse" or "drug resistance" phenomena that face the practicing oncologist on a daily basis and it serves as a translational reference for clinical applications. It covers the increasing evidence that impaired expression/activity of at least some of the DNA repair proteins account for tumor cell resistance to particular therapeutic agents. This book summarizes timely in-depth reviews covering the latest developments that have potential for translational and clinical applications and represents the first volume dedicated to the translational aspect of DNA repair in the clinic.