Inhibition of VEGF-A prevents the angiogenic switch and results in increased survival of Apc^sup +/min^ mice

Anti-VEGF-A monoclonal antibodies, in combination with chemotherapy, result in a survival benefit in patients with metastatic colorectal and non-small cell lung cancer, but little is known regarding the impact of anti-VEGF-A therapy on benign or premalignant tumors. The ... mice have been widely use...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2007-06, Vol.104 (25), p.10625
Main Authors: Korsisaari, Nina, Kasman, Ian M, rest, William F, Pal, Navneet
Format: Article
Language:English
Subjects:
Cell growth
Digestive system
Drug therapy
Genetics
Inhibitor drugs
Monoclonal antibodies
Rodents
Tumors
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Summary:Anti-VEGF-A monoclonal antibodies, in combination with chemotherapy, result in a survival benefit in patients with metastatic colorectal and non-small cell lung cancer, but little is known regarding the impact of anti-VEGF-A therapy on benign or premalignant tumors. The ... mice have been widely used as a model recapitulating early intestinal adenoma formation. To investigate whether tumor growth in ... mice is mediated by VEGF-A-dependent angiogenesis, we used two independent approaches to inhibit VEGF-A: monotherapy with a monoclonal antibody (Mab) targeting VEGF-A and genetic deletion of VEGF-A selectively in intestinal epithelial cells. Short-term (3 or 6 weeks) treatment with anti-VEGF-A Mab G6-31 resulted in a nearly complete suppression of adenoma growth throughout the small intestine. Growth inhibition by Mab G6-31 was associated with a decrease in vascular density. Long-term (up to 52 weeks) treatment with Mab G6-31 led to a substantial increase in median survival. Deletion of VEGF-A in intestinal epithelial cells of ... mice yielded a significant inhibition of tumor growth, albeit of lesser magnitude than that resulting from Mab 06-31 administration. These results establish that inhibition of VEGF-A signaling is sufficient for tumor growth cessation and confers a long-term survival benefit in an intestinal adenoma model. Therefore, VEGF-A inhibition may be a previously uncharacterized strategy for the prevention of the angiogenic switch and growth in intestinal adenomas. (ProQuest-CSA LLC: ... denotes formulae/symbols omitted.)
ISSN:0027-8424
1091-6490