Trending With Impact: CUDC907 Promotes Apoptosis of NF2 Schwannoma Cells

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July 28, 2022

Oncotarget published this trending research paper on July 19, 2022 in Volume 13, entitled, "CUDC907, a dual phosphoinositide-3 kinase/histone deacetylase inhibitor, promotes apoptosis of NF2 Schwannoma cells" by researchers from the Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL; Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL; Department of Pathology, University of Miami Miller School of Medicine, Miami, FL; Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL. DOI - https://doi.org/10.18632/oncotarget.28254 Correspondence to - Cristina Fernandez-Valle - cfv@ucf.edu Abstract Neurofibromatosis Type 2 (NF2) is a rare tumor disorder caused by pathogenic variants of the merlin tumor suppressor encoded by NF2. Patients develop vestibular schwannomas (VS), peripheral schwannomas, meningiomas, and ependymomas. There are no approved drug therapies for NF2. Previous work identified phosphoinositide-3 kinase (PI3K) as a druggable target. Here we screened PI3K pathway inhibitors for efficacy in reducing viability of human schwannoma cells. The lead compound, CUDC907, a dual histone deacetylase (HDAC)/PI3K inhibitor, was further evaluated for its effects on isolated and nerve-grafted schwannoma model cells, and primary VS cells. CUDC907 (3 nM IG50) reduced human merlin deficient Schwann cell (MD-SC) viability and was 5–100 fold selective for MD over WT-SCs. CUDC907 (10 nM) promoted cell cycle arrest and caspase-3/7 activation within 24 h in human MD-SCs. Western blots confirmed a dose-dependent increase in acetylated lysine and decreases in pAKT and YAP. CUDC907 decreased tumor growth rate by 44% in a 14-day treatment regimen, modulated phospho-target levels, and decreased YAP levels. In five primary VS, CUDC907 decreased viability, induced caspase-3/7 cleavage, and reduced YAP levels. Its efficacy correlated with basal phospho-HDAC2 levels. CUDC907 has cytotoxic activity in NF2 schwannoma models and primary VS cells and is a candidate for clinical trials. Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28254 Press release - https://www.oncotarget.com/news/pr/oncotarget-cudc-promotes-apoptosis-of-nf-schwannoma-cells/ Keywords - fimepinostat, Schwann cell, vestibular schwanomma, merlin, nerve allograft About Oncotarget Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

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