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Cell Biosci. 2017 Aug 3;7:37. doi: 10.1186/s13578-017-0165-3. eCollection 2017.

Isocitrate dehydrogenases in physiology and cancer: biochemical and molecular insight.

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1
Department of Pathology and Laboratory Medicine, King Fahad Specialist Hospital, 6830 Ammar Bin Thabit St, Al Muraikabat, Dammam, 32253 Saudi Arabia.

Abstract

Isocitrate dehydrogenases play important roles in cellular metabolism and cancer. This review will discuss how the roles of isoforms 1 and 2 in normal cell and cancer metabolism are distinct from those of isoform 3. It will also explain why, unlike 1 and 2, mutations in isoform 3 in tumor are not likely to be driver ones. A model explaining two important features of isocitrate dehydrogenases 1 and 2 mutations, their dominant negative effect and their mutual exclusivity, will be provided. The importance of targeting these mutations and the possibility of augmenting such therapy by targeting other cancer-related pathways will also be discussed.

KEYWORDS:

AML; Cancer; Dominant negative effect; Driver mutations; Glioma; IDH; Metabolism; Mutual exclusivity; Targeted therapy

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