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The implications of IDH mutations for cancer development and therapy.

Publication ,  Journal Article
Pirozzi, CJ; Yan, H
Published in: Nat Rev Clin Oncol
October 2021

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.

Duke Scholars

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Published In

Nat Rev Clin Oncol

DOI

EISSN

1759-4782

Publication Date

October 2021

Volume

18

Issue

10

Start / End Page

645 / 661

Location

England

Related Subject Headings

  • Neoplasms
  • Mutation
  • Molecular Targeted Therapy
  • Isocitrate Dehydrogenase
  • Humans
  • Cell Transformation, Neoplastic
  • Biomarkers, Tumor
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
 

Citation

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Pirozzi, C. J., & Yan, H. (2021). The implications of IDH mutations for cancer development and therapy. Nat Rev Clin Oncol, 18(10), 645–661. https://doi.org/10.1038/s41571-021-00521-0
Pirozzi, Christopher J., and Hai Yan. “The implications of IDH mutations for cancer development and therapy.Nat Rev Clin Oncol 18, no. 10 (October 2021): 645–61. https://doi.org/10.1038/s41571-021-00521-0.
Pirozzi CJ, Yan H. The implications of IDH mutations for cancer development and therapy. Nat Rev Clin Oncol. 2021 Oct;18(10):645–61.
Pirozzi, Christopher J., and Hai Yan. “The implications of IDH mutations for cancer development and therapy.Nat Rev Clin Oncol, vol. 18, no. 10, Oct. 2021, pp. 645–61. Pubmed, doi:10.1038/s41571-021-00521-0.
Pirozzi CJ, Yan H. The implications of IDH mutations for cancer development and therapy. Nat Rev Clin Oncol. 2021 Oct;18(10):645–661.

Published In

Nat Rev Clin Oncol

DOI

EISSN

1759-4782

Publication Date

October 2021

Volume

18

Issue

10

Start / End Page

645 / 661

Location

England

Related Subject Headings

  • Neoplasms
  • Mutation
  • Molecular Targeted Therapy
  • Isocitrate Dehydrogenase
  • Humans
  • Cell Transformation, Neoplastic
  • Biomarkers, Tumor
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis