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Cellular senescence and radiation-induced pulmonary fibrosis

Published:March 27, 2019DOI:https://doi.org/10.1016/j.trsl.2019.03.006

      Abstract

      Radiation-induced pulmonary fibrosis (RIPF) is a serious treatment complication that affects about 9%–30% cancer patients receiving radiotherapy for thoracic tumors. RIPF is characterized by progressive and irreversible destruction of lung tissues and deterioration of lung function, which can compromise quality of life and eventually lead to respiratory failure and death. Unfortunately, the mechanisms by which radiation causes RIPF have not been well established nor has an effective treatment for RIPF been developed. Recently, an increasing body of evidence suggests that induction of senescence by radiation may play an important role in RIPF and clearance of senescent cells (SnCs) with a senolytic agent, small molecule that can selectively kill SnCs, has the potential to be developed as a novel therapeutic strategy for RIPF. This review discusses some of these new findings to promote further study on the role of cellular senescence in RIPF and the development of senolytic therapeutics for RIPF.

      Abbreviations:

      AEC2 (type II alveolar epithelial cells), AECs (alveolar epithelial cells), APAF1 (apoptotic protease-activating factor 1), ASCs (alveolar stem cells), ATM (ataxia telangiectasia mutated), BAK (BCL-2 antagonist/killer), BAX (BCL-2-associated X protein), CRNB (cereblon), DDR (DNA damage response), DSB (double-strand break), HSCs (hematopoietic stem cells), IPF (idiopathic pulmonary fibrosis), IP (interfering peptide), IR (ionizing radiation), MAPK (mitogen-activated protein kinase), MOMP (mitochondrial outer membrane permeabilization), NOXs (NADPH oxidases), RIPF (radiation-induced pulmonary fibrosis), ROS (reactive oxygen species), rPAI-1 (recombinant truncated plasminogen activator inhibitor-1 protein), RT (radiotherapy), SASP (senescence-associated secretory phenotype), SCAPs (SnC antiapoptotic pathways), SnCs (senescent cells), TBI (total body irradiation), Trf2 (telomeric repeat-binding factor 2), VHL (von Hippel-Lindau tumor suppressor)
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