ZIA BC 010483 (ZIA) | |||
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Title | TEM5 Ligand Hunt | ||
Institution | NCI, Bethesda, MD | ||
Principal Investigator | St. Croix, Brad | NCI Program Director | N/A |
Cancer Activity | N/A | Division | CCR |
Funded Amount | $365,275 | Project Dates | 10/01/2002 - 00/00/0000 |
Fiscal Year | 2014 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Cancer (100.0%) | Vascular Disease (20.0%) | ||
Research Type | |||
Cancer Progression and Metastasis Systemic Therapies - Discovery and Development |
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Abstract | |||
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." |