Clinical usefulness of 2-hydroxyglutarate as a biomarker in IDH-mutant chondrosarcoma

Nakagawa, Makoto; Yamaguchi, Masayuki; Machida, Yukino; Hattori, Ayuna; Tanzawa, Fumie; Tsutsumi, Shinji; Kitabayashi, Issay; Kawai, Akira; Nakatani, Fumihiko

doi:10.1016/j.jbo.2022.100430

Cited by 4 publications

(1 citation statement)

References 35 publications

(52 reference statements)

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“…Mutation in IDH1/2 leads to the production of 2-hydroxyglutarate (2-HG), an oncometabolite that contributes to epigenetic changes such as histone methylation and DNA aberration [129]. Research conducted by Makoto Nakagawa et al revealed that 2-HG is a potentially significant biomarker for the presence of IDH mutations [130]. IDH mutations are more common in high-grade subtypes of chondrosarcoma, including DDCS [78,[125][126][127].…”

Section: Idh Mutationsmentioning

confidence: 99%

Dedifferentiated Chondrosarcoma from Molecular Pathology to Current Treatment and Clinical Trials

Zając,

Dróżdż,

Kisielewska

et al. 2023

Cancers

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Dedifferentiated chondrosarcoma (DDCS) is a rare subtype of chondrosarcoma, a primary cartilaginous malignant neoplasm. It accounts for up to 1–2% of all chondrosarcomas and is generally associated with one of the poorest prognoses among all chondrosarcomas with the highest risk of metastasis. The 5-year survival rates range from 7% to 24%. DDCS may develop at any age, but the average presentation age is over 50. The most common locations are the femur, pelvis humerus, scapula, rib, and tibia. The standard treatment for localised disease is surgical resection. Most patients are diagnosed in unresectable and advanced stages, and chemotherapy for localised and metastatic dedifferentiated DDCS follows protocols used for osteosarcoma.

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Section: Idh Mutationsmentioning

confidence: 99%

Dedifferentiated Chondrosarcoma from Molecular Pathology to Current Treatment and Clinical Trials

Zając,

Dróżdż,

Kisielewska

et al. 2023

Cancers

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A biosensor for D-2-hydroxyglutarate in frozen sections and intraoperative assessment of IDH mutation status

Zhang,

Yang,

Wang

et al. 2024

Biosensors and Bioelectronics

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Targeting Isocitrate Dehydrogenase (IDH) in Solid Tumors: Current Evidence and Future Perspectives

Carosi,

Broseghini,

Fabbri

et al. 2024

Cancers

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The isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) enzymes are involved in key metabolic processes in human cells, regulating differentiation, proliferation, and oxidative damage response. IDH mutations have been associated with tumor development and progression in various solid tumors such as glioma, cholangiocarcinoma, chondrosarcoma, and other tumor types and have become crucial markers in molecular classification and prognostic assessment. The intratumoral and serum levels of D-2-hydroxyglutarate (D-2-HG) could serve as diagnostic biomarkers for identifying IDH mutant (IDHmut) tumors. As a result, an increasing number of clinical trials are evaluating targeted treatments for IDH1/IDH2 mutations. Recent studies have shown that the focus of these new therapeutic strategies is not only the neomorphic activity of the IDHmut enzymes but also the epigenetic shift induced by IDH mutations and the potential role of combination treatments. Here, we provide an overview of the current knowledge about IDH mutations in solid tumors, with a particular focus on available IDH-targeted treatments and emerging results from clinical trials aiming to explore IDHmut tumor-specific features and to identify the clinical benefit of IDH-targeted therapies and their combination strategies. An insight into future perspectives and the emerging roles of circulating biomarkers and radiomic features is also included.

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Clinical usefulness of 2-hydroxyglutarate as a biomarker in IDH-mutant chondrosarcoma

Cited by 4 publications

References 35 publications

Dedifferentiated Chondrosarcoma from Molecular Pathology to Current Treatment and Clinical Trials

Dedifferentiated Chondrosarcoma from Molecular Pathology to Current Treatment and Clinical Trials

A biosensor for D-2-hydroxyglutarate in frozen sections and intraoperative assessment of IDH mutation status

Targeting Isocitrate Dehydrogenase (IDH) in Solid Tumors: Current Evidence and Future Perspectives

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