Targeting the cMET pathway augments radiation response without adverse effect on hearing in NF2 schwannoma models
Abstract
In patients with progressive vestibular schwannoma (VS), radiotherapy is associated with the risk of debilitating hearing loss. 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. In our newly developed cerebellopontine angle model of schwannomas that faithfully recapitulates the tumor-induced hearing loss, we demonstrate that cMET blockade sensitizes schwannomas to radiation therapy (RT) in neurofibromatosis type II schwannoma animal models without any adverse effects on hearing. Using an organoid brain slice culture model, cMET blockade inhibited the growth of patient-derived schwannomas. Our study provides the rationale and critical data for the clinical translation of combined cMET blockade with RT in patients with VSs.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 09, 2018
- Source ID
- 10.1073/pnas.1719966115
Entities
People
- Alona Muzikansky
- Anat Stemmer-Rachamimov
- Fu Zhao
- Gino B. Ferraro
- Hao Liu
- Jie Chen
- Jing Zhang
- Konstantina M. Stankovic
- Lei Xu
- Limeng Wu
- Lukas D Landegger
- Na Zhang
- Pinan Liu
- Rakesh Jain
- Scott R. Plotkin
- Takeshi Fujita
- Yanling Zhang
- Yanxia Zhao
- Yingchao Zhao
Organizations
- American Cancer Society
- Capital Medical University
- Harvard Medical School
- Massachusetts General Hospital
- National Cancer Institute
- National Institute on Deafness and Other Communication Disorders
- United States Department of Defense