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

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 gli...

Full description

Saved in:
Bibliographic Details
Published in:Cancers 2024-08, Vol.16 (15), p.2752
Main Authors: Carosi, Francesca, Broseghini, Elisabetta, Fabbri, Laura, Corradi, Giacomo, Gili, Riccardo, Forte, Valentina, Roncarati, Roberta, Filippini, Daria Maria, Ferracin, Manuela
Format: Article
Language:English
Subjects:
Biomarkers
Brain cancer
Brain tumors
Catalysis
Cell differentiation
Cell proliferation
Cells
Chemotherapy
Cholangiocarcinoma
Chondrosarcoma
Clinical trials
Development and progression
Enzymatic activity
Enzymes
Epigenetic inheritance
Epigenetics
Fatty acids
Genes
Glioma
Gliomas
Health aspects
Isocitrate dehydrogenase
Malignancy
Medical prognosis
Medical research
Medicine, Experimental
Metabolism
Mutation
Physiology
Radiomics
Serum levels
Solid tumors
Tricarboxylic acid cycle
Tumors
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers16152752