COX-2 inhibition potentiates antiangiogenic cancer therapy and prevents metastasis in preclinical models

Lihong Xu, Janine Stevens, Mary Beth Hilton, Steven Seaman, Thomas P. Conrads, Timothy D. Veenstra, Daniel Logsdon, Holly Morris, Deborah A. Swing, Nimit L. Patel, Joseph Kalen, Diana C. Haines, Enrique Zudaire, Brad St Croix*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

167 Scopus citations

Abstract

Antiangiogenic agents that block vascular endothelial growth factor (VEGF) signaling are important components of current cancer treatment modalities but are limited by alternative ill-defined angiogenesis mechanisms that allow persistent tumor vascularization in the face of continued VEGF pathway blockade. We identified prostaglandin E2 (PGE2) as a soluble tumor-derived angiogenic factor associated with VEGF-independent angiogenesis. PGE2 production in preclinical breast and colon cancer models was tightly controlled by cyclooxygenase-2 (COX-2) expression, and COX-2 inhibition augmented VEGF pathway blockade to suppress angiogenesis and tumor growth, prevent metastasis, and increase overall survival. These results demonstrate the importance of the COX-2/PGE2 pathway inmediating resistance to VEGF pathway blockade and could aid in the rapid development of more efficacious anticancer therapies.

Original languageEnglish
Article number242ra84
JournalScience Translational Medicine
Volume6
Issue number242
DOIs
StatePublished - 25 Jun 2014
Externally publishedYes

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