ArticleOncogene2024
Simultaneous inhibition of PI3K and PAK in preclinical models of neurofibromatosis type 2-related schwannomatosis.
Article in Oncogene, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 7 citations in OpenAlex.
- 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
- DeepDrugs: a mechanism-aware tri-linear attention framework for synergistic drug-combination prediction.Briefings in bioinformatics · 2026Article
- Phosphoproteomics identifies determinants of PAK inhibitor sensitivity in leukaemia cells.Cell communication and signaling : CCS · 2025Article
- NF2: An underestimated player in cancer metabolic reprogramming and tumor immunity.NPJ precision oncology · 2024Review
- Synergistic effect of PAK and Hippo pathway inhibitor combination in NF2-deficient Schwannoma.PloS one · 2024Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Neurofibromatosis Type 2 (NF2)-related schwannomatosis is a genetic disorder that causes development of multiple types of nervous system tumors. The primary and diagnostic tumor type is bilateral vestibular schwannoma. There is no cure or drug therapy for NF2. Recommended treatments include surgical resection and radiation, both of which can leave patients with severe neurological deficits or increase the risk of future malignant tumors. Results of our previous pilot high-throughput drug screen identified phosphoinositide 3-kinase (PI3K) inhibitors as strong candidates based on loss of viability of mouse merlin-deficient Schwann cells (MD-SCs). Here we used novel human schwannoma model cells to conduct combination drug screens. We identified a class I PI3K inhibitor, pictilisib and p21 activated kinase (PAK) inhibitor, PF-3758309 as the top combination due to high synergy in cell viability assays. Both single and combination therapies significantly reduced growth of mouse MD-SCs in an orthotopic allograft mouse model. The inhibitor combination promoted cell cycle arrest and apoptosis in mouse merlin-deficient Schwann (MD-SCs) cells and cell cycle arrest in human MD-SCs. This study identifies the PI3K and PAK pathways as potential targets for combination drug treatment of NF2-related schwannomatosis.
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