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Review
. 2012 Apr 15;72(8):1909-14.
doi: 10.1158/0008-5472.CAN-11-3406.

Anti-VEGF/VEGFR therapy for cancer: reassessing the target

Affiliations
Review

Anti-VEGF/VEGFR therapy for cancer: reassessing the target

Basel Sitohy et al. Cancer Res. .

Abstract

Judah Folkman recognized that new blood vessel formation is important for tumor growth and proposed antiangiogenesis as a novel approach to cancer therapy. Discovery of vascular permeability factor VEGF-A as the primary tumor angiogenesis factor prompted the development of a number of drugs that targeted it or its receptors VSports手机版. These agents have often been successful in halting tumor angiogenesis and in regressing rapidly growing mouse tumors. However, results in human cancer have been less impressive. A number of reasons have been offered for the lack of greater success, and, here, we call attention to the heterogeneity of the tumor vasculature as an important issue. Human and mouse tumors are supplied by at least 6 well-defined blood vessel types that arise by both angiogenesis and arterio-venogenesis. All 6 types can be generated in mouse tissues by an adenoviral vector expressing VEGF-A(164). Once formed, 4 of the 6 types lose their VEGF-A dependency, and so their responsiveness to anti-VEGF/VEGF receptor therapy. If therapies directed against the vasculature are to have a greater impact on human cancer, targets other than VEGF and its receptors will need to be identified on these resistant tumor vessels. .

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Conflict of interest statement

Conflict of interest: none

Figures

Figure 1
Figure 1
Schematic diagram of the angiogenic and arterio-venogenic blood vessels that are induced by Ad-VEGF-A164 in mouse tissues, identifying those that are (enclosed within the dash-lined box) or are not, susceptible to anti-VEGF therapy with rapamycin and VEGF Trap.

References

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