Journal
COLD SPRING HARBOR PERSPECTIVES IN MEDICINE
Volume 2, Issue 3, Pages -Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/cshperspect.a006486
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Funding
- Australian-American Fulbright Commission
- American Society for Clinical Oncology
- U.S. National Institutes of Health (NIH) [P01-CA80124, R01-CA85140, R01-CA115767, R01-CA126642]
- Federal Share/NCI Proton Beam Program Income
- National Foundation for Cancer Research
- Department of Defense [W81XWH-10-1-0016]
- AstraZeneca
- Dyax
- MedImmune
- Roche
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Pathological angiogenesis-driven byan imbalance of pro-and antiangiogenic signaling-is a hallmark of many diseases, both malignant and benign. Unlike in the healthy adult in which angiogenesis is tightly regulated, such diseases are characterized by uncontrolled new vessel formation, resulting in a microvascular network characterized by vessel immaturity, with profound structural and functional abnormalities. The consequence of these abnormalities is further modification of the microenvironment, often serving to fuel disease progression and attenuate response to conventional therapies. In this article, we present the vascular normalization hypothesis, which states that antiangiogenic therapy, by restoring the balance between pro-and antiangiogenic signaling, can induce a more structurally and functionally normal vasculature in a variety of diseases. We present the preclinical and clinical evidence supporting this concept and discuss how it has contributed to successful treatment of both solid tumors and several benign conditions.
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