Molecular Targeted Radiosensitizers: Opportunities and Challenges provides the reader with a comprehensive review of key pre-clinical research components required to identify effective radiosensitizing drugs. The book features discussions on the mechanisms and markers of clinical radioresistance, pre-clinical screening of targeted radiosensitizers, 3D radiation biology for studying radiosensitizers, in vivo determinations of local tumor control, genetically engineered mouse models for studying radiosensitizers, targeting the DNA damage response for radiosensitization, targeting tumor metabolism to overcome radioresistance, radiosensitizers in the era of immuno-oncology, and more. Additionally, the book features discussions on high-throughput drug screening, predictive biomarkers, pre-clinical tumor models, and the influence of the tumor microenvironment and the immune system, with a specific focus on the challenges radiation oncologists and medical oncologists currently face in testing radiosensitizers in human cancers.
Edited by two acclaimed experts in radiation biology and radiosensitizers, with thirteen chapters contributed by experts, this new volume presents an in-depth look at current developments within a rapidly moving field, with a look at where the field will be heading and providing comprehensive insight into the framework of targeted radiosensitzer development. Essential reading for investigators in cancer research and radiation biology.
Introduction to Molecular Targeted Radiosensitizers: Opportunities and Challenges.- Translating Targeted Radiosensitizers into the Clinic.- Cartography of the Radiogenome of Human Cancers.- Mechanisms and Markers of Clinical Radioresistance.- Preclinical Strategies for Testing of Targeted Radiosensitizers.- 3D Radiation Biology for Identifying Radiosensitizers.- Preclinical in vivo evaluation of novel radiosensitizers by local tumor control experiments.- Genetically Engineered Mouse Models for Studying Radiation Biology and Radiosensitizers.- Targeting the DNA Damage Response for Radiosensitization.- Targeting Tumor Metabolism to Overcome Radioresistance.-Targeting Tumor Hypoxia.- Normalizing the Tumor Microenvironment for Radiosensitization.- Radiosensitizers in the Era of Immuno-Oncology.- Index.
Henning Willers, M.D., is an Associate Professor of Radiation Oncology at Harvard Medical School and an Associate Radiation Oncologist in the Department of Radiation Oncology at Massachusetts General Hospital. He is also the Director of the Thoracic Radiation Oncology Program at Massachusetts General Hospital. As a clinician-scientist, Dr. Willers clinical efforts have focused on improving treatment outcomes for patients with lung cancer. His basic and translational research activities are directed at elucidating how lung cancers respond to radiation and radiosensitizing drugs, and specifically seeking to identify the signaling pathways that contribute to the radioresistance of KRAS-mutant lung adenocarcinoma. Dr. Willers lab also studies the DNA repair pathways that are increasingly recognized to be altered in lung cancer and other cancer types. The goal of these studies is to establish genomic as well as functional protein biomarkers that will allow clinicians to identify patients whose tumors will exhibit increased sensitivity to specific DNA damaging treatments, including proton beam radiation and PARP inhibitors.
Iris Eke is currently a researcher at Stanford University. She earned her M.D. at the Technical University Munich, Germany. During her Ph.D. in Experimental Radiation Oncology at the Technical University Dresden, Germany, she focused on the innovative concept to target cell-extracellular matrix interactions to overcome radio- and chemoresistance and elucidated several new mechanistic insights. At the National Cancer Institute, National Institute of Health, Dr. Eke studied the mechanisms of tumor adaptation after multifractionated radiotherapy with the goal to identify novel potential drug therapy targets involving radiation-induced target activation and DNA repair.
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