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Editorial
. 2023 May 1;29(9):1648-1650.
doi: 10.1158/1078-0432.CCR-23-0018.

Radiosensitization of IDH-Mutated Gliomas through ZMYND8 - a Pathway to Improved Outcomes

Sean Sachdev  1   2 , Crismita Dmello  2   3 , Adam M Sonabend  2   3
Affiliations
Editorial

Radiosensitization of IDH-Mutated Gliomas through ZMYND8 - a Pathway to Improved Outcomes

Sean Sachdev et al. Clin Cancer Res. .

Abstract

Isocitrate dehydrogenase 1-mutant (IDH1m) gliomas are recalcitrant tumors for which radiotherapy remains a standard treatment. A recent study identified ZMYND8 as a key mediator of radioresistance for IDH1m gliomas, and pharmacologic targeting of this pathway may heighten radiotherapy-induced tumor response, providing a prospect of improved clinical outcomes. See related article by Carney et al., p. 1763.

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Conflict of interest statement

Conflicts of Interest Declaration: A.M. Sonabend have received in kind and or funding support for research from Agenus, BMS, and Carthera. None of these relate to what is discussed on this manuscript.

Figures

Figure 1.
Figure 1.. Proposed mechanism of ZMYND8 mediated radioresistance in IDH mutant gliomas.
ZMYND8, which is upregulated in IDH1m gliomas interacts with HDAC1/2 and PARP complexes at the site of DNA damage, dampening the effect of radiation. However, treatment with IDH1m specific inhibitor AGI-5198 decreases the levels of ZMYND8 and hence repair of the damaged DNA. Similarly, knockdown/knockout of ZMYND8 or treatment with HDAC inhibitors (iHDAC) or PARP inhibitors (iPARP) can overcome the radioresistance in IDH1m gliomas. (Figure created with BioRender.com.)
See this image and copyright information in PMC

Comment in

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References

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