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Anti-VEGF treatment improves neurological function and augments radiation response in NF2 schwannoma model.

Authors :
Gao X
Zhao Y
Stemmer-Rachamimov AO
Liu H
Huang P
Chin S
Selig MK
Plotkin SR
Jain RK
Xu L
Source :
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2015 Nov 24; Vol. 112 (47), pp. 14676-81. Date of Electronic Publication: 2015 Nov 09.
Publication Year :
2015

Abstract

Hearing loss is the main limitation of radiation therapy for vestibular schwannoma (VS), and identifying treatment options that minimize hearing loss are urgently needed. Treatment with bevacizumab is associated with tumor control and hearing improvement in neurofibromatosis type 2 (NF2) patients; however, its effect is not durable and its mechanism of action on nerve function is unknown. We modeled the effect anti-VEGF therapy on neurological function in the sciatic nerve model and found that it improves neurological function by alleviating tumor edema, which may further improve results by decreasing muscle atrophy and increasing nerve regeneration. Using a cranial window model, we showed that anti-VEGF treatment may achieve these effects via normalizing the tumor vasculature, improving vessel perfusion, and delivery of oxygenation. It is known that oxygen is a potent radiosensitizer; therefore, we further demonstrated that combining anti-VEGF with radiation therapy can achieve a better tumor control and help lower the radiation dose and, thus, minimize radiation-related neurological toxicity. Our results provide compelling rationale for testing combined therapy in human VS.

Details

Language :
English
ISSN :
1091-6490
Volume :
112
Issue :
47
Database :
MEDLINE
Journal :
Proceedings of the National Academy of Sciences of the United States of America
Publication Type :
Academic Journal
Accession number :
26554010
Full Text :
https://doi.org/10.1073/pnas.1512570112