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Cancer Sci. 2017 Jan;108(1):151-155. doi: 10.1111/cas.13103.

Dual targeting of vascular endothelial growth factor and bone morphogenetic protein-9/10 impairs tumor growth through inhibition of angiogenesis.

Author information

1
Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
2
Oncology Team, Nanomedicine Group, Pharmaceutical Research Laboratories, Research and Development Group, Nippon Kayaku Co. Ltd., Tokyo, Japan.
3
Laboratory of Oncology, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
4
Department of Cellular Physiological Chemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
5
Department of Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

Abstract

Clinical development of anti-angiogenic agents has been a major landmark in cancer therapy for several types of cancers. Signals mediated by both vascular endothelial growth factor (VEGF) and bone morphogenetic protein (BMP)-9 and 10 have been implicated in tumor angiogenesis. However, previous studies have shown that targeting the individual signals was not sufficiently effective in retarding tumor growth in certain preclinical and clinical conditions. In the present study, we developed a novel decoy chimeric receptor that traps both VEGF and BMP-9/10. Single targeting of either VEGF or BMP-9/10 signals significantly reduced the formation of tumor vessels in a mouse xenograft model of human pancreatic cancer; however, it did not show significant therapeutic effects on tumor growth. In contrast, dual targeting of the angiogenic signals resulted in more significant inhibition of tumor angiogenesis, leading to delay of tumor growth. Our findings suggest that simultaneous blockade of VEGF and BMP-9/10 signals is a promising therapeutic strategy for the cancers that are resistant to anti-VEGF and BMP-9/10 therapies.

KEYWORDS:

ALK1; BMP-9/10; Fc-chimera; angiogenesis; vascular endothelial growth factor

PMID:
28133920
PMCID:
PMC5276835
DOI:
10.1111/cas.13103
[Indexed for MEDLINE]
Free PMC Article

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