Targeting the IDH2 Pathway in Acute Myeloid Leukemia

Clin Cancer Res. 2018 Oct 15;24(20):4931-4936. doi: 10.1158/1078-0432.CCR-18-0536. Epub 2018 May 16.

Abstract

Acute myeloid leukemia (AML) is an aggressive disease with a poor prognosis. A large percentage of patients succumb to this disease in spite of aggressive treatments with chemotherapy. Recent advances with mutational analysis led to the discovery of isocitrate dehydrogenase (IDH) mutations in AML. IDH2 is an enzyme that catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate; its mutated version leads to the accumulation of the oncometabolite (R)-2 hydroxyglutarate, which disrupts several cell processes and leads to a blockage in differentiation. Targeting IDH2 is compelling, as it is an early and stable mutation in AML. Enasidenib, a specific small-molecule inhibitor of IDH2, recently gained FDA approval for the treatment of patients with relapsed/refractory IDH2-mutated AML. In this review, we will focus on the indications and efficacy of enasidenib in the treatment of patients with IDH2-mutated AML. Clin Cancer Res; 24(20); 4931-6. ©2018 AACR.

Publication types

  • Review

MeSH terms

  • Aminopyridines / pharmacology
  • Aminopyridines / therapeutic use
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor
  • Drug Resistance, Neoplasm
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Isocitrate Dehydrogenase / metabolism*
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / etiology
  • Leukemia, Myeloid, Acute / metabolism*
  • Molecular Targeted Therapy*
  • Mutation
  • Prognosis
  • Recurrence
  • Signal Transduction / drug effects*
  • Treatment Outcome
  • Triazines / pharmacology
  • Triazines / therapeutic use

Substances

  • Aminopyridines
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Triazines
  • enasidenib
  • IDH2 protein, human
  • Isocitrate Dehydrogenase