Related Experiment Video

Updated: Feb 12, 2026

Visualizing Genetic Variants, Short Targets, and Point Mutations in the Morphological Tissue Context with an RNA In Situ Hybridization Assay
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Visualizing Genetic Variants, Short Targets, and Point Mutations in the Morphological Tissue Context with an RNA In Situ Hybridization Assay

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Targeting glutaminolysis in chondrosarcoma in context of the IDH1/2 mutation

Elisabeth F P Peterse1, Bertine Niessen1, Ruben D Addie1

  • 1Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.

British Journal of Cancer
|March 27, 2018
PubMed
Abstract

Insights

Targeting glutaminolysis with drugs like CB-839 and metformin shows promise for treating high-grade chondrosarcoma. These metabolic inhibitors are effective against chondrosarcoma cell lines, offering a potential new therapeutic strategy.

Area of Science:

  • Oncology
  • Metabolic Pathways
  • Cancer Therapeutics

Background:

  • Chondrosarcoma, a malignant cartilage tumor, often harbors IDH1/2 mutations.
  • IDH1/2 mutant cells show increased reliance on glutaminolysis.
  • Existing clinical trials explore glutaminolysis inhibitors (CB-839, metformin, chloroquine) for chondrosarcoma.

Purpose of the Study:

  • Evaluate the preclinical rationale for using glutaminolysis inhibitors in chondrosarcoma treatment.
  • Assess the efficacy of CB-839, metformin, phenformin, and chloroquine against chondrosarcoma.
  • Investigate the impact of these drugs on cellular metabolism and signaling pathways.

Main Methods:

  • Immunohistochemistry used to determine glutaminase expression in 120 cartilage tumors.
  • Ten chondrosarcoma cell lines treated with CB-839, metformin, phenformin, and chloroquine.
  • Analysis of mTOR activity and LC3B-II levels in response to treatment.

Main Results:

  • Glutaminase expression varied significantly with tumor grade, highest in high-grade chondrosarcomas.
  • Chondrosarcoma cell lines demonstrated sensitivity to glutaminolysis inhibition.
  • Metformin and phenformin reduced mTOR activity; metformin decreased LC3B-II levels, which chloroquine counteracted.

Conclusions:

  • Inhibiting glutaminolysis via CB-839, metformin, phenformin, or chloroquine presents a viable therapeutic strategy.
  • This approach is potentially effective for a subset of high-grade chondrosarcomas.
  • Treatment efficacy is independent of IDH1/2 mutation status.

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