ArticleAmerican journal of translational research2014
A chemical biology approach identified PI3K as a potential therapeutic target for neurofibromatosis type 2.
Article in American journal of translational research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 36 citations in OpenAlex.
- Rewiring mTOR signaling in Alzheimer's disease: emerging mTOR modulators beyond oncology.Bioscience reports · 2026Review
- A review of targeted therapies for NF2-related vestibular schwannoma: molecular pathogenesis, emerging therapeutics, and future clinical horizons.Journal of neuro-oncology · 2026Review
- Ex Vivo Characterization Studies Identify Candidate Therapies for the Individualized Care ofCancers · 2026Article
- Fimepinostat Promotes Apoptosis and Decreases Cytokine Secretion inInternational journal of molecular sciences · 2026Article
- Emerging systemic treatment strategies for vestibular schwannoma.Journal of neuro-oncology · 2026Review
- NF2-Related Schwannomatosis (NF2): Molecular Insights and Therapeutic Avenues.International journal of molecular sciences · 2024Review
- Simultaneous inhibition of PI3K and PAK in preclinical models of neurofibromatosis type 2-related schwannomatosis.Oncogene · 2024Article
- Autophagy Modulation in Therapeutic Strategy of Breast Cancer Drug Resistance.Journal of Cancer · 2024Review
- Germline Variants in Cancer Predisposition Genes in Pediatric Patients with Central Nervous System Tumors.International journal of molecular sciences · 2023Article
- Cotargeting Phosphoinositide 3-Kinase and Focal Adhesion Kinase Pathways Inhibits Proliferation of NF2 Schwannoma Cells.Molecular cancer therapeutics · 2023Article
- The genetic landscape and possible therapeutics of neurofibromatosis type 2.Cancer cell international · 2023Review
- Article
- Merlin-Deficient Schwann Cells Are More Susceptible to Radiation Injury than Normal Schwann Cells In Vitro.Journal of neurological surgery. Part B, Skull base · 2022Article
- CUDC907, a dual phosphoinositide-3 kinase/histone deacetylase inhibitor, promotes apoptosis of NF2 Schwannoma cells.Oncotarget · 2022Article
- Potential Molecular Biomarkers of Vestibular Schwannoma Growth: Progress and Prospects.Frontiers in oncology · 2021Review
- Characterization of a newly established schwannoma cell line from a sporadic vestibular schwannoma patient.American journal of translational research · 2021Article
- Peroxynitrite supports a metabolic reprogramming in merlin-deficient Schwann cells and promotes cell survival.The Journal of biological chemistry · 2019Article
- Preclinical assessment of MEK1/2 inhibitors for neurofibromatosis type 2-associated schwannomas reveals differences in efficacy and drug resistance development.Neuro-oncology · 2019Article
- Fluorescent Detection of Merlin-deficient Schwann Cells and Primary Human Vestibular Schwannoma Cells Using Sodium Fluorescein.Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology · 2018Article
- 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
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Mutations in the merlin tumor suppressor gene cause Neurofibromatosis type 2 (NF2), which is a disease characterized by development of multiple benign tumors in the nervous system. The current standard of care for NF2 calls for surgical resection of the characteristic tumors, often with devastating neurological consequences. There are currently no approved non-surgical therapies for NF2. In an attempt to identify much needed targets and therapeutically active compounds for NF2 treatment, we employed a chemical biology approach using ultra-high-throughput screening. To support this goal, we created a merlin-null mouse Schwann cell (MSC) line to screen for compounds that selectively decrease their viability and proliferation. We optimized conditions for 384-well plate assays and executed a proof-of-concept screen of the Library of Pharmacologically Active Compounds. Further confirmatory and selectivity assays identified phosphatidylinositol 3-kinase (PI3K) as a potential NF2 drug target. Notably, loss of merlin function is associated with activation of the PI3K/Akt pathway in human schwannomas. We report that AS605240, a PI3K inhibitor, decreased merlin-null MSC viability in a dose-dependent manner without significantly decreasing viability of control Schwann cells. AS605240 exerted its action on merlin-null MSCs by promoting caspase-dependent apoptosis and inducing autophagy. Additional PI3K inhibitors tested also decreased viability of merlin-null MSCs in a dose-dependent manner. In summary, our chemical genomic screen and subsequent hit validation studies have identified PI3K as potential target for NF2 therapy.
Indexed as
Identifiers
25360213PMC4212923W105668805What OpenQuestion holds
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.