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Science 7 January 2005:
Vol. 307. no. 5706, pp. 58 - 62
DOI: 10.1126/science.1104819
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Review

Normalization of Tumor Vasculature: An Emerging Concept in Antiangiogenic Therapy

Rakesh K. Jain

Solid tumors require blood vessels for growth, and many new cancer therapies are directed against the tumor vasculature. The widely held view is that these antiangiogenic therapies should destroy the tumor vasculature, thereby depriving the tumor of oxygen and nutrients. Here, I review emerging evidence supporting an alternative hypothesis—that certain antiangiogenic agents can also transiently "normalize" the abnormal structure and function of tumor vasculature to make it more efficient for oxygen and drug delivery. Drugs that induce vascular normalization can alleviate hypoxia and increase the efficacy of conventional therapies if both are carefully scheduled. A better understanding of the molecular and cellular underpinnings of vascular normalization may ultimately lead to more effective therapies not only for cancer but also for diseases with abnormal vasculature, as well as regenerative medicine, in which the goal is to create and maintain a functionally normal vasculature.

E. L. Steele Lab for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, and Harvard Medical School, Cox-7, 100 Blossom Street, Boston, MA 02114, USA. E-mail: jain{at}steele.mgh.harvard.edu

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R. Ansiaux, C. Baudelet, B. F. Jordan, N. Crokart, P. Martinive, J. DeWever, V. Gregoire, O. Feron, and B. Gallez (2006)
Cancer Res. 66, 9698-9704
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Randomized study of Paclitaxel and tamoxifen deposition into human brain tumors: implications for the treatment of metastatic brain tumors..
R. L. Fine, J. Chen, C. Balmaceda, J. N. Bruce, M. Huang, M. Desai, M. B. Sisti, G. M. McKhann, R. R. Goodman, J. S. Bertino Jr., et al. (2006)
Clin. Cancer Res. 12, 5770-5776
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Vaccination with viable human umbilical vein endothelial cells prevents metastatic tumors by attack on tumor vasculature with both cellular and humoral immunity..
X.-Y. Chen, W. Zhang, W. Zhang, S. Wu, F. Bi, Y.-J. Su, X.-Y. Tan, J.-N. Liu, and J. Zhang (2006)
Clin. Cancer Res. 12, 5834-5840
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