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Wild-Type IDH Enzymes as Actionable Targets for Cancer Therapy

Department of Molecular Biotechnology and Health Sciences, University of Torino, via Nizza 52, 10126 Torino, Italy
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Author to whom correspondence should be addressed.
Cancers 2019, 11(4), 563; https://doi.org/10.3390/cancers11040563
Received: 26 March 2019 / Revised: 12 April 2019 / Accepted: 16 April 2019 / Published: 19 April 2019
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Abstract

Isocitrate dehydrogenases (IDHs) are enzymes that catalyze the oxidative decarboxylation of isocitrate, producing α-ketoglutarate (αKG) and CO2. The discovery of IDH1 and IDH2 mutations in several malignancies has brought to the approval of drugs targeting IDH1/2 mutants in cancers. Here, we summarized findings addressing the impact of IDH mutants in rare pathologies and focused on the relevance of non-mutated IDH enzymes in tumors. Several pieces of evidence suggest that the enzymatic inhibition of IDHs may have therapeutic potentials also in wild-type IDH cancers. Moreover, IDHs inhibition could enhance the efficacy of canonical cancer therapies, such as chemotherapy, target therapy, and radiotherapy. However, further studies are required to elucidate whether IDH proteins are diagnostic/prognostic markers, instrumental for tumor initiation and maintenance, and could be exploited as targets for anticancer therapy. The development of wild-type IDH inhibitors is expected to improve our understanding of a potential non-oncogenic addition to IDH1/2 activities and to fully address their applicability in combination with other therapies. View Full-Text
Keywords: isocitrate dehydrogenase (IDH); wild-type IDH inhibitors; combination therapy; non-oncogenic addition; α-ketoglutarate (αKG); reactive oxygen species (ROS); DNA damage isocitrate dehydrogenase (IDH); wild-type IDH inhibitors; combination therapy; non-oncogenic addition; α-ketoglutarate (αKG); reactive oxygen species (ROS); DNA damage
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Bergaggio, E.; Piva, R. Wild-Type IDH Enzymes as Actionable Targets for Cancer Therapy. Cancers 2019, 11, 563.

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