Dual HDAC and PI3K Inhibition Abrogates NFκB- and FOXM1-Mediated DNA Damage Response to Radiosensitize Pediatric High-Grade Gliomas

Cancer Research
Sharmistha PalDaphne A Haas-Kogan

Abstract

Aberrant chromatin remodeling and activation of the PI3K pathway have been identified as important mediators of pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) pathogenesis. As inhibition of these pathways are promising therapeutic avenues and radiation is the only modality to prolong survival of patients with DIPG, we sought to explore radiosensitizing functions of such inhibition and to explore mechanisms of action of such agents. Here, we demonstrate that combined treatment with radiotherapy and CUDC-907, a novel first-in-class dual inhibitor of histone deacetylases (HDAC) and PI3K, evokes a potent cytotoxic response in pHGG and DIPG models. CUDC-907 modulated DNA damage response by inhibiting radiation-induced DNA repair pathways including homologous recombination and nonhomologous end joining. The radiosensitizing effects of CUDC-907 were mediated by decreased NFκB/Forkhead box M1 (FOXM1) recruitment to promoters of genes involved in the DNA damage response; exogenous expression of NFκB/FOXM1 protected from CUDC-907-induced cytotoxicity. Together, these findings reveal CUDC-907 as a novel radiosensitizer with potent antitumor activity in pHGG and DIPG and provide a preclinical rationale for t...Continue Reading

References

Apr 1, 1995·Molecular Biology of the Cell·G J Den HaeseK L Gould
Aug 11, 1998·Trends in Biochemical Sciences·P Baumann, S C West
Jul 16, 2003·Radiation Research·Gui-Rong DingJunji Miyakoshi
Jul 10, 2007·Acta Neuropathologica·David N LouisPaul Kleihues
Jul 16, 2009·Molecular Carcinogenesis·Carolin SchildGünter Schneider
Jul 18, 2009·International Journal of Cancer. Journal International Du Cancer·Dong BaiPeter K Vogt
Jan 16, 2010·The Journal of Biological Chemistry·Da-Jung JungWang-Jae Lee
Jun 14, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Changgeng QianMaurizio Voi
Feb 19, 2013·Future Oncology·David R Raleigh, Daphne A Haas-Kogan
May 30, 2013·Frontiers in Oncology·Tina Dasgupta, Daphne A Haas-Kogan
Jun 26, 2013·Nature Reviews. Cancer·Eric W-F LamChuay-Yeng Koo
Oct 8, 2013·Trends in Cell Biology·Michal Zimmermann, Titia de Lange
Dec 7, 2013·Neuro-oncology·Sabine MuellerDaphne A Haas-Kogan
Dec 12, 2013·Nature Reviews. Molecular Cell Biology·Stephanie Panier, Simon J Boulton
Aug 28, 2014·Cell Reports·Bo ZhaoBenjamin E Gewurz
Oct 8, 2014·Biochimica Et Biophysica Acta·Stefania ZonaEric W-F Lam
Jul 8, 2015·Nature Medicine·Giulia SiravegnaAlberto Bardelli
Aug 26, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Amar GajjarNicholas G Gottardo
Feb 3, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Lin LiJia-Fu Ji
Mar 16, 2016·Cancer Cell·Yanxin PeiRobert J Wechsler-Reya
Apr 2, 2016·Science Advances·Rishi R LullaRintaro Hashizume
Apr 7, 2016·Nature Communications·Hamid NikbakhtJavad Nazarian
May 7, 2016·Bioinformatics·Giovanni Y Di VeroliDuncan I Jodrell
Jul 1, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Angela NebbiosoLucia Altucci
Oct 16, 2016·Nucleic Acids Research·Wynand Paul Roos, Andrea Krumm
Apr 25, 2017·Cancer Cell·Surya NagarajaMichelle Monje

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Citations

Jun 17, 2020·Expert Review of Neurotherapeutics·James Felker, Alberto Broniscer
May 28, 2019·Neuro-oncology Advances·Raymond ChangUday B Maachani
Mar 23, 2020·Journal of Cell Communication and Signaling·Zhao-Jun LiFeng-Ze Wang
Aug 6, 2020·Frontiers in Cell and Developmental Biology·Alexandre PerlaRafael Roesler
Oct 3, 2020·International Journal of Molecular Sciences·Maya S Graham, Ingo K Mellinghoff
Sep 12, 2018·Cancers·Ying ZhangRoger Abounader
Nov 27, 2020·Journal of Experimental & Clinical Cancer Research : CR·Shejuan AnAmanda M Saratsis
Nov 19, 2020·The Journal of Clinical Endocrinology and Metabolism·S T Sharma
Dec 21, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kristina A ColeBrenda J Weigel
Jan 8, 2021·International Journal of Radiation Oncology, Biology, Physics·Joseph K SalamaDavid G Kirsch
Jan 6, 2021·Journal of Neuro-oncology·Brandon WummerCatherine Flores
Oct 30, 2020·Frontiers in Cell and Developmental Biology·Guo LiWei-Guo Zhu
Mar 7, 2021·Cancers·Hong-My NguyenDipongkor Saha
Feb 27, 2021·Clinical Epigenetics·Hong LiWenchu Lin
Apr 20, 2021·Frontiers in Oncology·Dennis S MetselaarEsther Hulleman

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