The implications of IDH mutations for cancer development and therapy.

Journal Article (Journal Article;Review)

Mutations in the genes encoding the cytoplasmic and mitochondrial forms of isocitrate dehydrogenase (IDH1 and IDH2, respectively; collectively referred to as IDH) are frequently detected in cancers of various origins, including but not limited to acute myeloid leukaemia (20%), cholangiocarcinoma (20%), chondrosarcoma (80%) and glioma (80%). In all cases, neomorphic activity of the mutated enzyme leads to production of the oncometabolite D-2-hydroxyglutarate, which has profound cell-autonomous and non-cell-autonomous effects. The broad effects of IDH mutations on epigenetic, differentiation and metabolic programmes, together with their high prevalence across a variety of cancer types, early presence in tumorigenesis and uniform expression in tumour cells, make mutant IDH an ideal therapeutic target. Herein, we describe the current biological understanding of IDH mutations and the roles of mutant IDH in the various associated cancers. We also present the available preclinical and clinical data on various methods of targeting IDH-mutant cancers and discuss, based on the underlying pathogenesis of different IDH-mutated cancer types, whether the treatment approaches will converge or be context dependent.

Full Text

Duke Authors

Cited Authors

  • Pirozzi, CJ; Yan, H

Published Date

  • October 2021

Published In

Volume / Issue

  • 18 / 10

Start / End Page

  • 645 - 661

PubMed ID

  • 34131315

Electronic International Standard Serial Number (EISSN)

  • 1759-4782

Digital Object Identifier (DOI)

  • 10.1038/s41571-021-00521-0

Language

  • eng

Conference Location

  • England