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

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.

authors

Gao X,Zhao Y,Stemmer-Rachamimov AO,Liu H,Huang P,Chin S,Selig MK,Plotkin SR,Jain RK,Xu L

doi

10.1073/pnas.1512570112

subject

Has Abstract

pub_date

2015-11-24 00:00:00

pages

14676-81

issue

47

eissn

0027-8424

issn

1091-6490

pii

1512570112

journal_volume

112

pub_type

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