Molecular biology and novel therapeutics for IDH mutant gliomas: The new era of IDH inhibitors.

Gliomas with Isocitrate dehydrogenase (IDH) mutation represent a discrete category of primary brain tumors with distinct and unique characteristics, behaviors, and clinical disease outcomes. IDH mutations lead to aberrant high-level production of the oncometabolite D-2-hydroxyglutarate (D-2HG), which act as a competitive inhibitor of enzymes regulating epigenetics, signaling pathways, metabolism, and various other processes. This review summarizes the significance of IDH mutations, resulting upregulation of D-2HG and the associated molecular pathways in gliomagenesis. With the recent finding of clinically effective IDH inhibitors in these gliomas, this article offers a comprehensive overview of the new era of innovative therapeutic approaches based on mechanistic rationales, encompassing both completed and ongoing clinical trials targeting gliomas with IDH mutations.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Daniel P. Cahill reports a relationship with Massachusetts Institute of Technology, Advise Connect Inspire, German Accelerator, Lilly, GlaxoSmithKline, Iconovir, Incephalo, Boston Pharmaceuticals, Servier, Boston Scientific and Pyramid Biosciences, Merck, US NIH and DoD. that includes: consulting or advisory, equity or stocks, and travel reimbursement. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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