VEGF Trap induces antiglioma effect at different stages of disease

¹ Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 USA
² Novartis Institutes for Biomedical Research, Emeryville, CA; Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591 USA
³ Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 USA
⁴ Department of Biostatistics and Applied Mathematics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030 USA

^* To whom correspondence should be addressed. E-mail: cmanzano{at}mdanderson.org.

	Abstract

Pathological angiogenesis is a hallmark of cancer, specifically of glioblastomas, the most malignant and common primary brain tumor. Vascular endothelial growth factor (VEGF) is the key protein in the regulation of the hypervascular phenotype of primary, malignant brain tumors. In this study, we tested VEGF Trap, a soluble decoy receptor for VEGF, in an intracranial glioma model. VEGF Trap was administered in short or prolonged schedules to human glioma-bearing animals at different stages of disease. Of importance, VEGF Trap treatment was efficacious in both initial and advanced phases of tumor development, by significantly increasing overall survival. Furthermore, this effect was enhanced in animals treated with more prolonged regimens. In addition, we observed the emergence of a VEGF Trap-resistant phenotype characterized by tumor growth and increased invasiveness. Our results suggest that VEGF Trap will be effective in treating both patients with recurrent or progressive resectable glioblastoma, and patients that have undergone extensive initial surgery. Finally, our results indicate that the clinical success of VEGF Trap may depend on a prolonged treatment in combined therapy aiming to simultaneously inhibit angiogenesis and tumor invasion.

Key Words: glioblastoma, Therapy, VEGF Trap, VEGF

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