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Updated: Mar 15, 2026

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
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IDH1 and IDH2 mutations as novel therapeutic targets: current perspectives

Johanna Mondesir1, Christophe Willekens2, Mehdi Touat3

  • 1Service d'Immunopathologie Clinique, Hôpital Saint Louis; CNRS UMR8104, INSERM U1016, Institut Cochin, Université Paris Descartes, Paris.

Journal of Blood Medicine
|September 14, 2016
PubMed

Insights

Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) enzymes create an oncometabolite, D-2-hydroxyglutarate (D-2HG), driving cancer. D-2HG disrupts cell metabolism and epigenetics, offering a target for novel cancer therapies.

Area of Science:

  • Biochemistry
  • Oncology
  • Molecular Biology

Background:

  • Isocitrate dehydrogenase 1 and 2 (IDH1/2) are crucial metabolic enzymes.
  • Mutations in IDH1/2 are hallmarks of specific cancers, including gliomas and hematologic malignancies.
  • These mutations lead to the production of the oncometabolite D-2-hydroxyglutarate (D-2HG).

Purpose of the Study:

  • To elucidate the role of IDH1/2 mutations in cancer development.
  • To understand the mechanism by which D-2HG contributes to oncogenesis.
  • To highlight D-2HG as a biomarker and therapeutic target.

Main Methods:

  • Analysis of IDH1/2 enzyme function in cancer cells.
  • Investigation of D-2HG's impact on cellular metabolism and epigenetic regulation.
  • Evaluation of D-2HG as a diagnostic and predictive biomarker.

Main Results:

  • IDH1/2 mutations result in excessive D-2HG accumulation.
  • D-2HG inhibits α-ketoglutarate-dependent dioxygenases, causing hypermethylation and blocking cell differentiation.
  • Elevated D-2HG levels are associated with IDH1/2 mutations and clinical response.

Conclusions:

  • IDH1/2 mutations drive oncogenesis through D-2HG production.
  • D-2HG interferes with epigenetic processes critical for cell differentiation.
  • Targeted inhibitors of mutant IDH1/2 enzymes represent a promising therapeutic strategy.
Keywords:
2-HGIDH1IDH2acute myeloid leukemiaepigeneticgliomaoncogenetargeted therapiestumor metabolism

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