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Review
. 2019 Apr 19;11(4):563.
doi: 10.3390/cancers11040563.

Wild-Type IDH Enzymes as Actionable Targets for Cancer Therapy

Elisa Bergaggio  1 , Roberto Piva  2
Affiliations
Review

Wild-Type IDH Enzymes as Actionable Targets for Cancer Therapy

Elisa Bergaggio et al. Cancers (Basel). .

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.

Keywords: DNA damage; combination therapy; isocitrate dehydrogenase (IDH); non-oncogenic addition; reactive oxygen species (ROS); wild-type IDH inhibitors; α-ketoglutarate (αKG).

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
IDH inhibition enhances canonical cancer therapies efficacy. Schematic representation of the underlying mechanisms that increase the response to cancer therapies in presence of IDH1/2 inhibition.
See this image and copyright information in PMC

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