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Anti-VEGF treatment improves neurological function and augments radiation response in NF2 schwannoma model.
- 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.
- Subjects :
- Animals
Antibodies pharmacology
Antibodies therapeutic use
Cell Line, Tumor
Disease Models, Animal
Dose-Response Relationship, Radiation
Edema complications
Edema pathology
Humans
Mice
Muscular Atrophy complications
Muscular Atrophy pathology
Nerve Regeneration drug effects
Neurofibromatosis 2 physiopathology
Neurofibromin 2 deficiency
Neurofibromin 2 metabolism
Neuroma, Acoustic blood supply
Neuroma, Acoustic drug therapy
Radiation Tolerance drug effects
Rotarod Performance Test
Sciatic Nerve drug effects
Sciatic Nerve pathology
Sciatic Nerve ultrastructure
Signal Transduction drug effects
Treatment Outcome
Vascular Endothelial Growth Factor A metabolism
Neurofibromatosis 2 complications
Neuroma, Acoustic physiopathology
Neuroma, Acoustic radiotherapy
Vascular Endothelial Growth Factor A antagonists & inhibitors
Subjects
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