Abstract

THERAPEUTIC ADVANCES WITH IVOSIDENIB: TARGETING IDH1 MUTATIONS IN CANCER

R. Jona Methusula*, Meenuga Chitra and Suvarna Sravani

ABSTRACT

Isocitrate dehydrogenase 1 (IDH1) mutations represent a critical molecular driver in a subset of hematologic and solid malignancies, most notably acute myeloid leukemia (AML) and cholangiocarcinoma. These mutations result in the production of the oncometabolite 2- hydroxyglutarate (2-HG), which disrupts cellular differentiation via epigenetic dysregulation. Ivosidenib, a first-in-class, oral small-molecule inhibitor of mutant IDH1, has demonstrated significant clinical activity, leading to regulatory approval in multiple indications. This review summarizes the molecular basis for targeting IDH1, the pharmacologic properties of ivosidenib, key clinical trial evidence,safety profile, resistance mechanisms, and future directions. The integration of ivosidenib into precision oncology represents a paradigm shift in the management of IDH1-mutant cancers, although challenges remain in resistance and accessibility.

Keywords: Ivosidenib, IDH1 mutation, acute myeloid leukemia, cholangiocarcinoma, targeted therapy, 2-hydroxyglutarate.