Evaluating ivosidenib for the treatment of relapsed/refractory AML: design, development, and place in therapy.

ABSTRACT: Improvements in the last decade in understanding the molecular mechanisms underlying acute myeloid leukemia (AML) have emphasized that treatment regimens should be personalized with agents that can selectively target genetic abnormalities if present. Neomorphic mutations in isoform 1 of isocitrate dehydrogenase (IDH1) result in the formation of the onco-metabolite R-2-hydroxyglutarate, which drives leukemic transformation by affecting processes such as chromatin remodeling, the cellular defense against oxidative stress and cell survival. Preclinical studies with small molecule inhibitors have validated mutant IDH1 as a molecular target, and a recent Phase 1 clinical trial with the first mutant IDH1 inhibitor ivosidenib has prompted approval by the US Food and Drug Association

SUBMITTER: Nassereddine S 

PROVIDER: S-EPMC6314316 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature