Contributors; Chapter 1: Improving the€Therapeutic Ratio of€Radiotherapy by Targeting the€DNA Damage Response; Introduction; The DNA Damage Response (DDR); Detection of€Radiation-Induced DNA Damage and€Initiation of€DDR; Ataxia Telangiectasia Mutated (ATM); Ataxia Telangiectasia and€Rad 3 Related (ATR); DNA-Dependent Protein Kinase (DNA-PK); Cell Cycle Checkpoint Control; DNA Repair Processes; Non-homologous End Joining (NHEJ); Homologous Recombination (HR); Poly (ADP-Ribose) Polymerases (PARPs); DNA Damage Response as€a€Therapeutic Target; PARP Inhibition.

ATM Inhibition ATR Inhibition; Chk1 Inhibition; Inhibition of€NHEJ; Rad51 Inhibition; Combination DDR Inhibition; DDR Kinase Inhibition and€Cancer Stem Cell Theory; Combining Radiotherapy and€DDR Kinase Inhibition in€the€Clinic; Clinical Trials of€DDR Kinase Inhibition; Biomarkers; Conclusion; References; Chapter 2: Receptor Tyrosine Kinases as€Targets for€Enhancing Tumor Radiosensitivity; Introduction; EGFR; VEGF/VEGFR; c-Met; Other RTKs; Conclusion; References; Chapter 3: Histone Deacetylase Inhibitors and€Tumor Radiosensitization; Introduction.

Histone Acetylation and Deacetylation Histone Acetylation and€Metabolism; Inhibitors of€Histone Deacetylation; HDAC Inhibitors and€Radiosensitization; In Vitro Radiosensitization; In Vivo Radiosensitization; Tumor Versus Normal Cells; Clinical Application of€HDAC Inhibitors and€Radiotherapy; Conclusion; References; Chapter 4: Radioprotection as€a€Method to€Enhance the€Therapeutic Ratio of€Radiotherapy; Background; Methods to€Improve the€Therapeutic Index of€Radiotherapy; Radioprotectors; Amifostine; Nitroxides; Other Candidate Radioprotectors; Radiation Mitigators.

Total Body Exposures Dermatitis; Fibrosis; Central Nervous System Injury; Treatment; Challenges; References; Chapter 5: Application of€Functional Molecular Imaging in€Radiation Oncology; Introduction; Principles of€Established and€Emerging Advanced Molecular Imaging Technology; CT Imaging; Radionuclide Imaging; PET and€SPECT; MRI; Imaging of€Tumor Metabolism; 18F-FDG PET/CT; Hyperpolarized Metabolic MR; Imaging Cellular Proliferation; MRSI; Imaging Tumor Microenvironment; Methods for€Evaluating Hypoxia; DCE-MRI; BOLD-MRI; EPRI and€OMRI; Conclusion; Future Perspective.

Current cancer therapies are focused on three general strategies: modifying intrinsic radiosensitivity via molecular targeting, manipulating microenvironmental factors to enhance tumor susceptibility to radiation, and improving delivery of radiation to critical tumor locations while sparing normal tissues. The goal of this volume is to describe a number of promising approaches corresponding to each strategy. In general, research in radiation oncology tends to be siloed into fundamental biology, physics or treatment delivery. The strategies for improving therapeutic ratio encompassed in this book will involve each of these components of radiation oncology. Thus, they will illustrate the variety of disparate approaches available for potentially improving the efficacy of radiotherapy, which may then stimulate discussion across disciplines and foster further translational investigations. Although a goal of each chapter will be to highlight advances within an approach, of equal importance will be the delineation of barriers to successful clinical application and how to overcome or minimize such impediments. Along these lines, because therapeutic ratio incorporates both tumor and normal tissue radio response, a point of emphasis will be the mechanistic rationale for selectively modifying tumor (sensitization) or normal cells (protection). Finally, whereas the literature is replete with studies describing potential targets/strategies for increasing the therapeutic ratio for radiotherapy, this book will focus on those supported by in vivo data consistent with impending translational application along with those that are already being evaluated in the clinic.