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Potential of serum microRNAs as biomarkers of radiation injury and tools for individualization of radiotherapy

  • Author Footnotes
    1 These authors contributed equally to this work.
    Bartłomiej Tomasik
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland

    Postgraduate School of Molecular Medicine, Warsaw Medical University, Warsaw, Poland
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Justyna Chałubińska-Fendler
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Radiology Therapeutic Centre, Zgorzelec, Poland
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  • Dipanjan Chowdhury
    Correspondence
    Reprint requests: Dipanjan Chowdhury, Department of Radiation Oncology, Harvard Medical School, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115; Wojciech Fendler, Department of Biostatistics and Translational Medicine, Medical University of Lodz, 15 Mazowiecka Street, 92-215 Lodz, Poland.
    Affiliations
    Department of Radiation Oncology, Harvard Medical School, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
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  • Wojciech Fendler
    Correspondence
    Reprint requests: Dipanjan Chowdhury, Department of Radiation Oncology, Harvard Medical School, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115; Wojciech Fendler, Department of Biostatistics and Translational Medicine, Medical University of Lodz, 15 Mazowiecka Street, 92-215 Lodz, Poland.
    Affiliations
    Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland

    Department of Radiation Oncology, Harvard Medical School, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.

      Abstract

      Due to tremendous technological advances, radiation oncologists are now capable of personalized treatment plans and deliver the dose in a highly precise manner. However, a crucial challenge is how to escalate radiation doses to cancer cells while reducing damage to surrounding healthy tissues. This determines the probability of achieving therapeutic success whilst safeguarding patients from complications. The current dose constraints rely on observational data. Therefore, incidental toxicity observed in a minority of patients limits the admissible dose thresholds for the whole population, theoretically narrowing down the curative potential of radiotherapy. Future tools for measurements of individual's radiosensitivity before and during treatment would allow proper treatment personalization. Variation in tissue tolerance is at least partially genetically-determined and recent progress in the field of molecular biology raises the possibility that novel assays will allow to predict the response to ionizing radiation. Recently, microRNAs have garnered interest as stable biomarkers of tumor radiation response and normal-tissue toxicity. Preclinical studies in mice and nonhuman primates have shown that serum circulating microRNAs can be used to accurately distinguish pre- and postirradiation states and predict the biological impact of high-dose irradiation. First reports from human studies are also encouraging, however biology-driven precision radiation oncology, which tailors treatment to individual patient's needs, still remains to be translated into clinical studies. In this review, we summarize current knowledge about the potential of serum microRNAs as biodosimeters and biomarkers for radiation injury to lung and hematopoietic cells.

      Abbreviations:

      AGO proteins (Argonaute proteins), CTCAE (common toxicity criteria for adverse events), Dicer (Helicase with RNase motif), Drosha (ribonuclease III enzyme involved in miRNA maturation), DSB (double strand breaks), DVH (dose-volume histogram), EORTC (European Organization for Research and Treatment for Cancer), GWAS (Genome Wide Association Studies), HDL (high density lipoprotein), ICRP (International Commission on Radiological Protection), IL (interleukin), IR (ionizing radiation), LASSO (least absolute shrinkage and selection operator), LSF (late side effects), miRNA (microRNA (ribonucleic acid)), NPM1 (nucleophosmine 1), NTCP (normal tissue complication probability), pri-miRNA (primary miRNA), pre-miRNA (precursor-miRNA), QUANTEC (Quantitative Analyses of Normal Tissue Effects in the Clinic), RAPPER study (Radiogenomics: Assessment of Polymorphisms for Predicting the Effects of Radiotherapy study), RILT (radiation-induced lung toxicity), RISC (RNA-induced silencing complex), RNAse (ribonuclease), ROS (reactive oxygen species), RP (radiation pneumonitis), RT (radiotherapy), RTOG (Radiation Therapy Oncology Group), siRNA (small interfering RNA), SNP (single nucleotide polymorphism), SOMA (subjective, objective, management, analytic), TD 5/5 (the probability of 5% complication within 5 years after radiotherapy), TD 50/5 (the probability of 50% complication within 5 years after radiotherapy), TGF-β (transforming growth factor beta), Vx (percentage of volume receiving x dose), RNA (ribonucleic acid), MIP (macrophage inflammatory protein), MCP (monocyte chemoattractant protein 1), TRBP (TAR RNA binding protein)
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