Biological Role and Therapeutic Potential of IDH Mutations in Cancer.

Journal Article (Journal Article;Review)

Hotspot mutations in isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) occur in a variety of myeloid malignancies and solid tumors. Mutant IDH proteins acquire a neomorphic enzyme activity to produce the putative oncometabolite D-2-hydroxyglutarate, which is thought to block cellular differentiation by competitively inhibiting α-ketoglutarate-dependent dioxygenases involved in histone and DNA demethylation. Small-molecule inhibitors of mutant IDH1 and IDH2 have been developed and are progressing through pre-clinical and clinical development. In this review, we provide an overview of mutant IDH-targeted therapy and discuss a number of important recent pre-clinical studies using models of IDH-mutant solid tumors.

Full Text

Duke Authors

Cited Authors

  • Waitkus, MS; Diplas, BH; Yan, H

Published Date

  • August 13, 2018

Published In

Volume / Issue

  • 34 / 2

Start / End Page

  • 186 - 195

PubMed ID

  • 29805076

Pubmed Central ID

  • PMC6092238

Electronic International Standard Serial Number (EISSN)

  • 1878-3686

Digital Object Identifier (DOI)

  • 10.1016/j.ccell.2018.04.011


  • eng

Conference Location

  • United States