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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 hypothesisthat 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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- Bevacizumab for the Treatment of Epithelial Ovarian Cancer: Will This Be Its Finest Hour?.
- S. B. Kaye (2007)
J. Clin. Oncol.
25, 5150-5152
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- Inhibition of Protein Kinase C{beta} by Enzastaurin Enhances Radiation Cytotoxicity in Pancreatic Cancer.
- A. C. Spalding, R. Watson, M. E. Davis, A. C. Kim, T. S. Lawrence, and E. Ben-Josef (2007)
Clin. Cancer Res.
13, 6827-6833
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- Biological Therapy and Other Novel Therapies in Early-Stage Disease: Are They Appropriate?.
- A. Grothey (2007)
Clin. Cancer Res.
13, 6909s-6912s
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- Caveolin-1 Is Critical for the Maturation of Tumor Blood Vessels through the Regulation of Both Endothelial Tube Formation and Mural Cell Recruitment.
- J. DeWever, F. Frerart, C. Bouzin, C. Baudelet, R. Ansiaux, P. Sonveaux, B. Gallez, C. Dessy, and O. Feron (2007)
Am. J. Pathol.
171, 1619-1628
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- EphB4 Overexpression in B16 Melanoma Cells Affects Arterial-Venous Patterning in Tumor Angiogenesis.
- X. Huang, Y. Yamada, H. Kidoya, H. Naito, Y. Nagahama, L. Kong, S.-Y. Katoh, W.-l. Li, M. Ueno, and N. Takakura (2007)
Cancer Res.
67, 9800-9808
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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
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- 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
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- 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
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- 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
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- 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
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- 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
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- 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
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- 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
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- 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
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- 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
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- 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
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