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Review
. 2018 Apr;37(15):1949-1960.
doi: 10.1038/s41388-017-0077-z. Epub 2018 Jan 25.

Wild-type and mutated IDH1/2 enzymes and therapy responses

Remco J Molenaar  1   2   3 , Jaroslaw P Maciejewski  4 , Johanna W Wilmink  5 , Cornelis J F van Noorden  6
Affiliations
Review

Wild-type and mutated IDH1/2 enzymes and therapy responses

Remco J Molenaar et al. Oncogene. 2018 Apr.

Erratum in

Abstract

Isocitrate dehydrogenase 1 and 2 (IDH1/2) are key enzymes in cellular metabolism, epigenetic regulation, redox states, and DNA repair. IDH1/2 mutations are causal in the development and/or progression of various types of cancer due to supraphysiological production of D-2-hydroxyglutarate. In various tumor types, IDH1/2-mutated cancers predict for improved responses to treatment with irradiation or chemotherapy. The present review discusses the molecular basis of the sensitivity of IDH1/2-mutated cancers with respect to the function of mutated IDH1/2 in cellular processes and their interactions with novel IDH1/2-mutant inhibitors. Finally, lessons learned from IDH1/2 mutations for future clinical applications in IDH1/2 wild-type cancers are discussed.

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Conflict of interest statement

J.P.M. has received honoraria, has performed consultancy, and has served as a speaker on behalf of Celgene. The remaining authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Effects of IDH1/2 mutations and d-2HG accumulation on cellular metabolism, redox states, and DNA damage repair. ALKBH alkylation repair homolog, ATM ataxia-telangiectasia mutated, ATP5 adenosine triphosphate synthase, CoA coenzyme A, COX cytochrome c oxidase, d-2HG d-2-hydroxyglutarate, ETC electron transport chain, FOXO forkhead box proteins, HuR human antigen R, IDH isocitrate dehydrogenase, KDM lysine histone demethylase, NAD(P) nicotinamide dinucleotide (phosphate), NAD(P)H nicotinamide dinucleotide (phosphate), reduced, NAM nicotinamide, NAMPT nicotinamide phosphoribosyltransferase, NMN nicotinamide mononucleotide, NRF2 nuclear factor (erythroid-derived 2)-like, ROS reactive oxygen species
Fig. 2
Fig. 2
Biochemical reactions of IDH1 and IDH2 wild type and mutant enzymes. The forward reaction is an oxidative decarboxylation, while the reverse reaction is a reductive carboxylation
See this image and copyright information in PMC

References

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