Abstract
Background: IDH1 and IDH2 (isocitrate dehydrogenase 1 and 2) are metabolic enzymes mutated in subsets of solid and hematological tumors. Mutations in IDH1 or IDH2 generate high levels of the 2-HG (2-hydroxyglutarate) oncometabolite that promotes de-differentiation, stemness and tumorigenesis. Inhibition of mutant IDH1or IDH2 decreases 2-HG production and induces re-differentiation of tumor cells. First generation IDH inhibitors received FDA approval for the treatment of subsets of AML and cholangiocarcinoma patients, but extent and duration of response are limited in these patients and no targeted options are available for the other IDH1/ IDH2 mutant solid tumors.
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