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Purine synthesis as a target for radiation resistance in molecular glioblastoma

  • Connor J. Kinslow
    Affiliations
    Department of Radiation Oncology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, 622 West 168th Street, BNH B-11, New York, NY 10032, United States
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  • Kunal R. Chaudhary
    Affiliations
    Department of Radiation Oncology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, 622 West 168th Street, BNH B-11, New York, NY 10032, United States
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  • Pavan S. Upadhyayula
    Affiliations
    Department of Radiation Oncology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, 622 West 168th Street, BNH B-11, New York, NY 10032, United States
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  • Tony J.C. Wang
    Affiliations
    Department of Radiation Oncology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, 622 West 168th Street, BNH B-11, New York, NY 10032, United States
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  • Ramon C. Sun
    Affiliations
    Department of Molecular and Cellular Biochemistry and Markey Cancer Center, University of Kentucky College of Medicine, Lexington, KY 40536, United States
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  • Simon K. Cheng
    Correspondence
    Corresponding author.
    Affiliations
    Department of Radiation Oncology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, 622 West 168th Street, BNH B-11, New York, NY 10032, United States
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Published:April 08, 2021DOI:https://doi.org/10.1016/j.jns.2021.117439
      Glioblastoma (GBM) is the most common primary brain cancer and considered invariably fatal. Despite decades of research, there have been few innovations in treatment that have improved survival [
      • Stupp R.
      • et al.
      Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma.
      ,
      • Stupp R.
      • et al.
      Effect of tumor-treating fields plus maintenance Temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial.
      ]. Gliomas and GBMs have historically been classified histologically until 2016, when the World Health Organization (WHO) instituted an additional molecular classification system based on isocitrate dehydrogenase (IDH) mutational status and 1p19q chromosomal codeletion [
      • Louis D.N.
      • et al.
      The 2016 World Health Organization classification of tumors of the central nervous system: a summary.
      ,
      Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas.
      ,
      • Kinslow C.J.
      • Canoll P.
      • Cheng S.K.
      • Wang T.J.C.
      Misclassification of diffuse gliomas — Letter.
      ]. Around 70% percent of gliomas and 5–7% of primary GBMs harbor mutations in IDH [
      • Parsons D.W.
      • et al.
      An integrated genomic analysis of human glioblastoma multiforme.
      ,
      • Yan H.
      • et al.
      IDH1 and IDH2 mutations in gliomas.
      ]. IDH-mutant tumors are thought to be more sensitive to chemotherapy and radiotherapy, although this has yet to be translated into differences in treatment recommendations.

      Keywords

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