Antiangiogenic agents that block vascular endothelial growth factor (VEGF) signaling are important components of current cancer treatmentmodalities but are limited by alternative ill-defined angiogenesismechanisms 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.
| Xu, Lihong; Stevens, Janine; Hilton, Mary Beth et al. (2014) COX-2 inhibition potentiates antiangiogenic cancer therapy and prevents metastasis in preclinical models. Sci Transl Med 6:242ra84 |
| Cullen, Mike; Elzarrad, Mohammed K; Seaman, Steven et al. (2011) GPR124, an orphan G protein-coupled receptor, is required for CNS-specific vascularization and establishment of the blood-brain barrier. Proc Natl Acad Sci U S A 108:5759-64 |
