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• W2594708898 startingPage "379" @default.
• W2594708898 abstract "Somatic mutations in the isocitrate dehydrogenase (IDH) 1 and 2 genes have been described in multiple hematologic and solid tumors, and confer a gain of function, permitting the production of the oncometabolite (R)-2-hydroxyglutarate (2-HG). 2-HG accumulation induces DNA and histone hypermethylation and altered gene expression, ultimately resulting in a block in cellular differentiation. Proof-of-concept preclinical work demonstrated that targeted inhibition of the mutant IDH (mIDH) enzyme is a feasible therapeutic strategy, based on the hypothesis that inhibition of the mIDH enzyme blocks 2-HG production, resulting in an appropriate methylation state and the onset of cellular differentiation. Clinical development programs for targeted inhibitors are underway, and preliminary data in patients with mIDH acute myeloid leukemia suggest that these inhibitors act as differentiation agents. Here we review the use of differentiation agents for the treatment of hematologic and solid tumors and discuss the preclinical and early clinical evidence that mIDH inhibitors mediate antitumor effects through the induction of differentiation." @default.
• W2594708898 created "2017-03-16" @default.
• W2594708898 creator A5053897548 @default.
• W2594708898 creator A5066934816 @default.
• W2594708898 date "2017-03-06" @default.
• W2594708898 modified "2023-10-18" @default.
• W2594708898 title "Targeted Differentiation Therapy with Mutant IDH Inhibitors: Early Experiences and Parallels with Other Differentiation Agents" @default.
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