ArticleThe Laryngoscope2012
Preclinical validation of AR42, a novel histone deacetylase inhibitor, as treatment for vestibular schwannomas.
Article in The Laryngoscope, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- Emerging Molecular Insights and Therapeutic Directions in Neurofibromatosis Type 1 and NF2-Related Schwannomatosis.International journal of molecular sciences · 2026Review
- Evaluation of the orally bioavailable 4-phenylbutyrate-tethered trichostatin A analogue AR42 in models of spinal muscular atrophy.Scientific reports · 2023Article
- Updates on Tumor Biology in Vestibular Schwannoma.Otolaryngologic clinics of North America · 2023Review
- [Prospects of Drug Therapy of Vestibular Schwannoma].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2022Review
- Early phase clinical studies of AR-42, a histone deacetylase inhibitor, for neurofibromatosis type 2-associated vestibular schwannomas and meningiomas.Laryngoscope investigative otolaryngology · 2021Article
- A phase 1 trial of the histone deacetylase inhibitor AR-42 in patients with neurofibromatosis type 2-associated tumors and advanced solid malignancies.Cancer chemotherapy and pharmacology · 2021Article
- A Review of Drug Therapy in Vestibular Schwannoma.Drug design, development and therapy · 2021Review
- KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer.Cancer cell · 2020Article
- A Xenograft Model of Vestibular Schwannoma and Hearing Loss.Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology · 2018Article
- Computational repositioning and preclinical validation of mifepristone for human vestibular schwannoma.Scientific reports · 2018Article
- The Role of Tumor Necrosis Factor Alpha (TNFα)in Hearing Loss and Vestibular Schwannomas.Current otorhinolaryngology reports · 2018Article
- Traditional and systems biology based drug discovery for the rare tumor syndrome neurofibromatosis type 2.PloS one · 2018Article
- Tumor-Penetrating Delivery of siRNA against TNFα to Human Vestibular Schwannomas.Scientific reports · 2017Article
- Sulforaphane, a natural component of broccoli, inhibits vestibular schwannoma growth in vitro and in vivo.Scientific reports · 2016Article
- Role of Merlin/NF2 inactivation in tumor biology.Oncogene · 2016Review
- Efficacy of Combined Histone Deacetylase and Checkpoint Kinase Inhibition in a Preclinical Model of Human Burkitt Lymphoma.Molecular medicine (Cambridge, Mass.) · 2015Article
- Bevacizumab decreases vestibular schwannomas growth rate in children and teenagers with neurofibromatosis type 2.Journal of neuro-oncology · 2015Article
- Mechanisms and clinical significance of histone deacetylase inhibitors: epigenetic glioblastoma therapy.Anticancer research · 2015Review
- Histone deacetylase inhibition rescues structural and functional brain deficits in a mouse model of Kabuki syndrome.Science translational medicine · 2014Article
- Primary culture of human vestibular schwannomas.Journal of visualized experiments : JoVE · 2014Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
objectives/hypothesisRecent studies indicate that vestibular schwannomas (VSs) rely on phosphatidylinositol 3-kinase/AKT activation to promote cell proliferation and survival; therefore, targeting AKT may provide new therapeutic options. We have previously shown that AR42, a novel histone deacetylase inhibitor, potently suppresses VS growth in vitro at doses correlating with AKT inactivation. The objectives of the current study were translational: 1) to examine the end biologic effects of AR42 on tumor growth in vivo, 2) to validate AKT as its in vivo molecular target, 3) to determine whether AR42 penetrates the blood-brain barrier (BBB), and 4) to study the pharmacotoxicity profile of AR42. STUDY
designIn vivo mouse studies.
methodsAR42 was dosed orally in murine schwannoma allografts and human VS xenografts. Magnetic resonance imaging was used to quantify changes in tumor volume, and intracellular molecular targets were analyzed using immunohistochemistry. BBB penetration was assayed, and both blood-chemistry measurements and histology studies were used to evaluate toxicity.
resultsGrowth of schwannoma implants was dramatically decreased by AR42 at doses correlating with AKT dephosphorylation, cell cycle arrest, and apoptosis. AR42 penetrated the BBB, and wild-type mice fed AR42 for 6 months behaved normally and gained weight appropriately. Blood-chemistry studies and organ histology performed after 3 and 6 months of AR42 treatment demonstrated no clinically significant abnormalities.
conclusionsAR42 suppresses schwannoma growth at doses correlating with AKT pathway inhibition. This orally bioavailable drug penetrates the BBB, is well tolerated, and represents a novel candidate for translation to human VS clinical trials.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.