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Radiotherapy is an effective treatment strategy for cancer, but a significant proportion of patients experience radiation-induced toxicity due to damage to normal tissue in the irradiation field. The use of chemical or biological approaches aimed at reducing or preventing normal tissue toxicity induced by radiotherapy is a long-held goal. Hypoxia-inducible factors (HIFs) regulate the production of factors that may protect several cellular compartments affected by radiation-induced toxicity. Pharmacological inhibitors of prolyl hydroxylase domain-containing enzymes (PHDs), which result in stabilization of HIFs, have recently been proposed as a new class of radioprotectors. In this review, radiation-induced toxicity in the gastrointestinal (GI) tract and the main cellular compartments studied in this context will be discussed. The effects of PHD inhibition on GI radioprotection will be described in detail.

Original publication

DOI

10.1172/JCI84432

Type

Journal article

Journal

J Clin Invest

Publication Date

03/10/2016

Volume

126

Pages

3708 - 3715

Keywords

Animals, Basic Helix-Loop-Helix Transcription Factors, Gastrointestinal Tract, Humans, Neoplasms, Prolyl Hydroxylases, Prolyl-Hydroxylase Inhibitors, Protein Stability, Radiation Injuries, Radiation-Protective Agents, Signal Transduction