In vivo method for establishing synergy between antibodies to epidermal growth factor receptor and vascular endothelial growth factor receptor-2.
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.
Tonra
James R
JR
ImClone Systems Inc, New York, NY, USA.
Prewett
Marie
M
Corcoran
Erik
E
Hicklin
Daniel J
DJ
Zhu
Zhenping
Z
D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004357:Drug Synergism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
D000906:Antibodies; D066246:ErbB Receptors; D040301:Vascular Endothelial Growth Factor Receptor-2