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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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The Addition of AG-013736 to Fractionated Radiation Improves Tumor Response without Functionally Normalizing the Tumor Vasculature.
B. M. Fenton and S. F. Paoni (2007)
Cancer Res. 67, 9921-9928
   Abstract »    Full Text »    PDF »
Reply.
F. D. Kolodgie, J. Narula, C. Yuan, A. V. Finn, H. K. Gold, and R. Virmani (2007)
J. Am. Coll. Cardiol. 50, 1521
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Drug Resistance and the Solid Tumor Microenvironment.
O. Tredan, C. M. Galmarini, K. Patel, and I. F. Tannock (2007)
J Natl Cancer Inst 99, 1441-1454
   Abstract »    Full Text »    PDF »
Peroxiredoxin 1 Interacts with Androgen Receptor and Enhances Its Transactivation.
S.-Y. Park, X. Yu, C. Ip, J. L. Mohler, P. N. Bogner, and Y.-M. Park (2007)
Cancer Res. 67, 9294-9303
   Abstract »    Full Text »    PDF »
Tumor Necrosis Factor {alpha} Mediates Homogeneous Distribution of Liposomes in Murine Melanoma that Contributes to a Better Tumor Response.
A. L.B. Seynhaeve, S. Hoving, D. Schipper, C. E. Vermeulen, G. aan de Wiel-Ambagtsheer, S. T. van Tiel, A. M.M. Eggermont, and T. L.M. ten Hagen (2007)
Cancer Res. 67, 9455-9462
   Abstract »    Full Text »    PDF »
Treatment of metastatic renal cancer with capsid-modified oncolytic adenoviruses.
K. Guse, T. Ranki, M. Ala-Opas, P. Bono, M. Sarkioja, M. Rajecki, A. Kanerva, T. Hakkarainen, and A. Hemminki (2007)
Mol. Cancer Ther. 6, 2728-2736
   Abstract »    Full Text »    PDF »
Antiangiogenics: The Potential Role of Integrating This Novel Treatment Modality With Chemoradiation for Solid Cancers.
D. G. Duda, R. K. Jain, and C. G. Willett (2007)
J. Clin. Oncol. 25, 4033-4042
   Abstract »    Full Text »    PDF »
Use of Molecular Biomarkers for Predicting the Response to Radiotherapy With or Without Chemotherapy.
O. Riesterer, L. Milas, and K. K. Ang (2007)
J. Clin. Oncol. 25, 4075-4083
   Abstract »    Full Text »    PDF »
Radiosensitization and Modulation of p44/42 Mitogen-Activated Protein Kinase by 2-Methoxyestradiol in Prostate Cancer Models.
E. V. Casarez, M. E. Dunlap-Brown, M. R. Conaway, and G. P. Amorino (2007)
Cancer Res. 67, 8316-8324
   Abstract »    Full Text »    PDF »
Hypoxia modulation and radiosensitization by the novel dual EGFR and VEGFR inhibitor AEE788 in spontaneous and related allograft tumor models.
C. Oehler-Janne, W. Jochum, O. Riesterer, A. Broggini-Tenzer, G. Caravatti, V. Vuong, and M. Pruschy (2007)
Mol. Cancer Ther. 6, 2496-2504
   Abstract »    Full Text »    PDF »
A Mechanistic Perspective of Monoclonal Antibodies in Cancer Therapy Beyond Target-Related Effects.
S. E. Strome, E. A. Sausville, and D. Mann (2007)
Oncologist 12, 1084-1095
   Abstract »    Full Text »    PDF »
Visualization of Hypoxia in Microscopic Tumors by Immunofluorescent Microscopy.
X.-F. Li, S. Carlin, M. Urano, J. Russell, C. C. Ling, and J. A. O'Donoghue (2007)
Cancer Res. 67, 7646-7653
   Abstract »    Full Text »    PDF »


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