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Normal tissues toxicities triggered by combined anti-angiogenic and radiation therapies: hurdles might be ahead.

Abstract：

BACKGROUND:Combined-modality therapy is a promising approach to improve the therapeutic index of radiotherapy. However, these improvements could come at the cost of increased toxicities. Clinical trials evaluating anti-tumour efficacy of bevacizumab combined with radiotherapy have encountered unexpected side effects. This study is the first systematic evaluation of normal tissue toxicity triggered by anti-angiogenic agents combined with radiation therapy in mice. METHODS:Effect of a mouse anti-VEGF antibody was monitored on acute toxicity studying radiation-induced intestinal ulceration (12 Gy TBI); on subacute toxicity using a model of oral mucositis (16.5 Gy); on late radiation injuries by monitoring lung fibrosis (bleomycin and 19 Gy). RESULTS:Combination of irradiation with anti-VEGF antibody enhanced intestinal damages with severe epithelial ulcerations, had no adverse impact on oral mucositis and dramatically worsened the fibrotic picture induced by bleomycin and irradiation to the lung. INTERPRETATION:These reports bring to light the important questions about safety and underscore the need for appropriate preclinical modelling of the impact on normal tissues of novel drug-radiation regimens. Our findings also highlight the complexity of anti-VEGF action, which could in defined conditions exert tissue-specific protection. The findings indicate that the combination of targeted drugs with radiotherapy should be approached with caution.

journal_name

Br J Cancer

journal_title

British journal of cancer

authors

Mangoni M,Vozenin MC,Biti G,Deutsch E

doi

10.1038/bjc.2012.236

subject

Has Abstract

pub_date

2012-07-10 00:00:00

pages

308-14

issue

2

eissn

0007-0920

issn

1532-1827

pii

bjc2012236

journal_volume

107

pub_type

杂志文章

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