IDH mutation in glioma: molecular mechanisms and potential therapeutic targets

Isocitrate dehydrogenase (IDH) enzymes catalyse the oxidative decarboxylation of isocitrate and therefore play key roles in the Krebs cycle and cellular homoeostasis. Major advances in cancer genetics over the past decade have revealed that the genes encoding IDHs are frequently mutated in a variety...

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Vydáno v:British journal of cancer Ročník 122; číslo 11; s. 1580 - 1589
Hlavní autoři: Han, Sue, Liu, Yang, Cai, Sabrina J., Qian, Mingyu, Ding, Jianyi, Larion, Mioara, Gilbert, Mark R., Yang, Chunzhang
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 26.05.2020
Nature Publishing Group
Témata:
631/208/737
631/80
Acute myeloid leukemia
Animals
Biomedical and Life Sciences
Biomedicine
Brain Neoplasms - genetics
Cancer Research
Cell Transformation, Neoplastic - genetics
Cholangiocarcinoma
Chondrosarcoma
Decarboxylation
Drug Resistance
Epidemiology
Glioma
Glioma - genetics
Humans
Isocitrate dehydrogenase
Isocitrate Dehydrogenase - genetics
Leukemia
Molecular Medicine
Molecular modelling
Mutants
Mutation
Oncology
Review
Review Article
Therapeutic applications
Thyroid cancer
Thyroid carcinoma
Tricarboxylic acid cycle
Tumorigenesis
ISSN:0007-0920, 1532-1827, 1532-1827
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Shrnutí:Isocitrate dehydrogenase (IDH) enzymes catalyse the oxidative decarboxylation of isocitrate and therefore play key roles in the Krebs cycle and cellular homoeostasis. Major advances in cancer genetics over the past decade have revealed that the genes encoding IDHs are frequently mutated in a variety of human malignancies, including gliomas, acute myeloid leukaemia, cholangiocarcinoma, chondrosarcoma and thyroid carcinoma. A series of seminal studies further elucidated the biological impact of the IDH mutation and uncovered the potential role of IDH mutants in oncogenesis. Notably, the neomorphic activity of the IDH mutants establishes distinctive patterns in cancer metabolism, epigenetic shift and therapy resistance. Novel molecular targeting approaches have been developed to improve the efficacy of therapeutics against IDH-mutated cancers. Here we provide an overview of the latest findings in IDH-mutated human malignancies, with a focus on glioma, discussing unique biological signatures and proceedings in translational research.
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ISSN:0007-0920
1532-1827
1532-1827
DOI:10.1038/s41416-020-0814-x