COX-2 Inhibition Potentiates Antiangiogenic Cancer Therapy and Prevents Metastasis in Preclinical Models

Overview

Journal Sci Transl Med

Specialties General Medicine
Science

Date 2014 Jun 27

PMID 24964992

Citations 104

Authors

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

Affiliations

Soon will be listed here.

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 in mediating resistance to VEGF pathway blockade and could aid in the rapid development of more efficacious anticancer therapies.

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