Related Experiment Video

Updated: Dec 12, 2025

Metabolic Mapping: Quantitative Enzyme Cytochemistry and Histochemistry to Determine the Activity of Dehydrogenases in Cells and Tissues
08:36

Metabolic Mapping: Quantitative Enzyme Cytochemistry and Histochemistry to Determine the Activity of Dehydrogenases in Cells and Tissues

Published on: May 26, 2018

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Isocitrate dehydrogenase variants in cancer - Cellular consequences and therapeutic opportunities

Shuang Liu1, Tom Cadoux-Hudson1, Christopher J Schofield1

  • 1Chemistry Research Laboratory, Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.

Current Opinion in Chemical Biology
|August 11, 2020
PubMed

Insights

Mutations in isocitrate dehydrogenase (IDH1 and IDH2) genes alter cell metabolism, leading to elevated d-2-hydroxyglutarate (d-2HG), a cancer biomarker. Therapeutic strategies targeting these IDH variants are under development.

Area of Science:

  • Biochemistry
  • Oncology
  • Metabolic pathways

Background:

  • Cancer cells exhibit altered metabolism, frequently linked to mutations in metabolic enzyme genes.
  • Isocitrate dehydrogenase 1 (IDH1) is the most commonly mutated metabolic gene in cancer.
  • Mutations in IDH1 and IDH2 disrupt normal metabolism, affecting 2-oxoglutarate and NADPH production.

Purpose of the Study:

  • To provide an overview of cancer-associated IDH variants.
  • To discuss the metabolic consequences of elevated d-2-hydroxyglutarate (d-2HG).
  • To summarize therapeutic approaches targeting IDH variants and identify future research directions.

Main Methods:

  • Literature review of cancer-associated IDH variants.
  • Analysis of metabolic alterations due to IDH mutations.
  • Summary of current therapeutic strategies and research gaps.

Main Results:

  • Cancer-associated IDH variants impair wild-type function and promote d-2HG production.
  • Elevated d-2HG levels serve as a biomarker in certain cancers.
  • IDH1 and IDH2 variants are actively pursued as medicinal chemistry targets.

Conclusions:

  • Understanding IDH mutations and their metabolic impact is crucial for cancer therapy.
  • Targeting IDH variants offers a promising therapeutic avenue.
  • Further research is needed to fully elucidate the role of IDH mutations in cancer and optimize treatments.
Keywords:
2-Hydroxyglutarate2-oxoglutarateAcute myeloid leukaemiaAlpha-ketoglutarateCancer metabolismEpigeneticsGliomaHypoxia-inducible factorIsocitrate dehydrogenaseJmjC demethylase

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