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Sci Transl Med. 2014 Jun 25;6(242):242ra84. doi: 10.1126/scitranslmed.3008455.

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

Author information

1
Tumor Angiogenesis Section, Mouse Cancer Genetics Program (MCGP), National Cancer Institute (NCI) at Frederick, National Institutes of Health, Frederick, MD 21702, USA.
2
Tumor Angiogenesis Section, Mouse Cancer Genetics Program (MCGP), National Cancer Institute (NCI) at Frederick, National Institutes of Health, Frederick, MD 21702, USA. Basic Research Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
3
Laboratory of Proteomics and Analytical Technologies, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
4
Basic Research Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
5
Transgenic Core Facility, MCGP, NCI, Frederick, MD 21702, USA.
6
Small Animal Imaging Program/LASP, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
7
Pathology/Histotechnology Laboratory, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
8
Tumor Angiogenesis Section, Mouse Cancer Genetics Program (MCGP), National Cancer Institute (NCI) at Frederick, National Institutes of Health, Frederick, MD 21702, USA. stcroix@ncifcrf.gov.

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.

Comment in

PMID:
24964992
PMCID:
PMC6309995
DOI:
10.1126/scitranslmed.3008455
[Indexed for MEDLINE]
Free PMC Article

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