Precision Oncology in Lower-Grade Gliomas: Promises and Pitfalls of Therapeutic Strategies Targeting IDH-Mutations.

ABSTRACT: Mutations in isocitrate dehydrogenase (IDH)1 and its homolog IDH2 are considered an earliest "driver" genetic event during gliomagenesis, representing now the molecular hallmark of lower-grade gliomas (LGGs). IDH-mutated genes encode for a neomorphic enzyme that converts α-ketoglutarate to the oncometabolite D-2-hydroxyglutarate (2-HG), which accumulates to high concentrations and alters cellular epigenetics and metabolism. Targeting IDH mutations is the first attempt to apply "precision oncology" in LGGs. Two distinct strategies have been proposed so far and are under intense clinical investigation: (i) reducing the amount of intratumoral 2-HG by directly blocking the function of mutant IDH enzyme; (ii) exploiting the selective epigenetic and metabolic cellular vulnerabilities as a conseq

SUBMITTER: Persico P 

PROVIDER: S-EPMC8909346 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature