Abstract
Targeted therapy for cancer is shifting towards an approach of inhibiting multiple pathways, justified in part by the ability of cancer cells to overcome the inhibition of a single pathway. However the literature is replete with preclinical data supporting the anticancer potential of numerous combinations of targeted agents, making it difficult to select the combination strategies to invest in through clinical development. One characteristic of a combination strategy that can be utilized for prioritization is synergy. Synergy indicates that the effect of the combination is greater than that predicted from the monotherapy potencies. Here we describe a detailed method for establishing synergy between two treatments in vivo. We utilized this method to establish that antibodies targeting the epidermal growth factor receptor and vascular endothelial growth factor receptor-2 are synergistic with regard to antitumor effects, in a BxPC-3 subcutaneous xenograft model for pancreatic cancer.
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Acknowledgments
The authors are very grateful to Nancy R. Mendell, Ph.D. and Xu Jiang for their significant efforts in deriving the statistical method for establishing synergy and writing the software included as a supplement, in the Department of Applied Mathematics and Statistics at the State University of New York at Stony Brook. In addition, the authors would like to thank Rajiv Bassi and Shannon Mitchel for their contributions towards the development of the reported techniques.
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© 2009 Humana Press, a part of Springer Science+Business Media, LLC
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Tonra, J.R., Prewett, M., Corcoran, E., Hicklin, D.J., Zhu, Z. (2009). In Vivo Method for Establishing Synergy Between Antibodies to Epidermal Growth Factor Receptor and Vascular Endothelial Growth Factor Receptor-2. In: Dimitrov, A. (eds) Therapeutic Antibodies. Methods in Molecular Biology™, vol 525. Humana Press. https://doi.org/10.1007/978-1-59745-554-1_30
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DOI: https://doi.org/10.1007/978-1-59745-554-1_30
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