ArticleProceedings of the National Academy of Sciences of the United States of America2018
Targeting the cMET pathway augments radiation response without adverse effect on hearing in NF2 schwannoma models.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 46 citations in OpenAlex.
- A Novel Serum miRNA Panel (miR-145, miR-34a, and miR-222) for Schwannoma Diagnosis.Biochemical genetics · 2026Article
- Deciphering and Targeting the Schwannoma-Neuron-Macrophage Crosstalk for the Treatment of Schwannomatosis and Associated Pain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Characterizing the effects of anti-PD1 immunotherapy on ataxia in a vestibular schwannoma mouse model.Journal of neuro-oncology · 2026Article
- Targeted and Personalized Therapy for Difficult Benign Brain Tumors: A Review.Journal of personalized medicine · 2026Review
- NKG2D upregulation sensitizes tumors to combined anti-PD1 and anti-VEGF therapy and prevents hearing loss.Nature communications · 2026Article
- Inhibition of focal adhesion kinase impairs tumor formation and preserves hearing in a murine model of NF2-related schwannomatosis.Science advances · 2026Article
- Advancements in Preclinical Models forCancers · 2026Review
- A cochlea-sparing strategy for non-invasive control of intracranial schwannomas via peripheral irradiation and anti-PD-1 therapy enhanced by STING activation.Theranostics · 2026Article
- The molecular biology of NF2/Merlin on tumorigenesis and development.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- Integrating Ataxia Evaluation into Tumor-Induced Hearing Loss Model to Comprehensively Study NF2-Related Schwannomatosis.Cancers · 2024Article
- Single-cell multi-omic analysis of the vestibular schwannoma ecosystem uncovers a nerve injury-like state.Nature communications · 2024Article
- Article
- The genetic landscape and possible therapeutics of neurofibromatosis type 2.Cancer cell international · 2023Review
- Advances in Targeted Therapy for Neurofibromatosis Type 2 (NF2)-Associated Vestibular Schwannomas.Current oncology reports · 2023Review
- The comparable tumour microenvironment in sporadic andBrain communications · 2023Article
- The Genomics of Auditory Function and Disease.Annual review of genomics and human genetics · 2022Review
- A Critical Overview of Targeted Therapies for Vestibular Schwannoma.International journal of molecular sciences · 2022Review
- Qu-Du-San-Jie decoction induces growth inhibition and vascular normalization in NF2-associated vestibular schwannoma.Frontiers in pharmacology · 2022Article
- Case Report: Extensive Temporal Bone Invasion in a Giant Vestibular Schwannoma.Frontiers in surgery · 2022Article
- Losartan prevents tumor-induced hearing loss and augments radiation efficacy in NF2 schwannoma rodent models.Science translational medicine · 2021Article
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Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
Abstract
Neurofibromatosis type II (NF2) is a disease that needs new solutions. Vestibular schwannoma (VS) growth causes progressive hearing loss, and the standard treatment, including surgery and radiotherapy, can further damage the nerve. There is an urgent need to identify an adjunct therapy that, by enhancing the efficacy of radiation, can help lower the radiation dose and preserve hearing. The mechanisms underlying deafness in NF2 are still unclear. One of the major limitations in studying tumor-induced hearing loss is the lack of mouse models that allow hearing testing. Here, we developed a cerebellopontine angle (CPA) schwannoma model that faithfully recapitulates the tumor-induced hearing loss. Using this model, we discovered that cMET blockade by crizotinib (CRZ) enhanced schwannoma radiosensitivity by enhancing DNA damage, and CRZ treatment combined with low-dose radiation was as effective as high-dose radiation. CRZ treatment had no adverse effect on hearing; however, it did not affect tumor-induced hearing loss, presumably because cMET blockade did not change tumor hepatocyte growth factor (HGF) levels. This cMET gene knockdown study independently confirmed the role of the cMET pathway in mediating the effect of CRZ. Furthermore, we evaluated the translational potential of cMET blockade in human schwannomas. We found that human NF2-associated and sporadic VSs showed significantly elevated HGF expression and cMET activation compared with normal nerves, which correlated with tumor growth and cyst formation. Using organoid brain slice culture, cMET blockade inhibited the growth of patient-derived schwannomas. Our findings provide the rationale and necessary data for the clinical translation of combined cMET blockade with radiation therapy in patients with NF2.
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