Isocitrate dehydrogenase mutations: New opportunities for translational research

Young Sam Keum, Bu Young Choi

Research output: Contribution to journalReview articlepeer-review

7 Scopus citations

Abstract

Over the last decade, comprehensive genome-wide sequencing studies have enabled us to find out unexpected genetic alterations of metabolism in cancer. An example is the identification of arginine missense mutations of isocitrate dehydrogenases-1 and -2 (IDH1/2) in glioma, acute myeloid leukemia (AML), chondrosarcomas, and cholangiocarcinoma. These alterations are closely associated with the production of a new stereospecific metabolite, (R)-2-hydroxyglutarate (R-2HG). A large number of follow-up studies have been performed to address the molecular mechanisms of IDH1/2 mutations underlying how these events contribute to malignant transformation. In the meanwhile, the development of selective mutant IDH1/2 chemical inhibitors is being actively pursued in the scientific community and pharmaceutical industry. The present review article briefly discusses the important findings that highlight the molecular mechanisms of IDH1/2 mutations in cancer and provides a current status for development of selective mutant IDH1/2 chemical inhibitors.

Original languageEnglish
Pages (from-to)266-270
Number of pages5
JournalBMB Reports
Volume48
Issue number5
DOIs
StatePublished - 2015

Keywords

  • (R)-2-hydroxyglutarate (R-2HG)
  • Cancer metabolism
  • Isocitrate (ICT)
  • Isocitrate dehydrogenases (IDHs)
  • α-ketoglutarate (α-KG)

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