Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Antiangiogenic Therapy: A Universal Chemosensitization Strategy for Cancer?
Robert S. Kerbel
For more than 50 years, a major goal of research in cancer therapeuticshas been to develop universally effective agents that rendercancer cells more sensitive to cytotoxic chemotherapy withoutsubstantially increasing toxicity to normal cells. The resultsof recent clinical trials indicate that certain antiangiogenicdrugs may produce this long-sought effect. Here, I describethree distinct mechanisms that may help to explain the chemosensitizingactivity of these drugs: normalizing tumor vasculature, preventingrapid tumor cell repopulation, and augmenting the antivasculareffects of chemotherapy. I then discuss how these potentialmechanisms might be exploited to maximize therapeutic efficacy.
Sunnybrook Health Sciences Centre, Departments of Medical Biophysics and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M4N 3M5, Canada.
The editors suggest the following Related Resources on Science sites:
In Science Magazine
INTRODUCTION TO SPECIAL ISSUE
Paula A. Kiberstis and John Travis (26 May 2006) Science312 (5777), 1157.
[DOI: 10.1126/science.312.5777.1157] |Summary »|PDF »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Tumor Angiogenesis.
R. S. Kerbel (2008)
N. Engl. J. Med.
358, 2039-2049
|Full Text »|PDF »
Antiangiogenic Therapy with Mammalian Target of Rapamycin Inhibitor RAD001 (Everolimus) Increases Radiosensitivity in Solid Cancer.
P. C. Manegold, C. Paringer, U. Kulka, K. Krimmel, M. E. Eichhorn, R. Wilkowski, K.-W. Jauch, M. Guba, and C. J. Bruns (2008)
Clin. Cancer Res.
14, 892-900
|Abstract »|Full Text »|PDF »
Modulation of the antitumor activity of metronomic cyclophosphamide by the angiogenesis inhibitor axitinib.
[18F]Galacto-RGD Positron Emission Tomography for Imaging of {alpha}v{beta}3 Expression on the Neovasculature in Patients with Squamous Cell Carcinoma of the Head and Neck.
A. J. Beer, A.-L. Grosu, J. Carlsen, A. Kolk, M. Sarbia, I. Stangier, P. Watzlowik, H.-J. Wester, R. Haubner, and M. Schwaiger (2007)
Clin. Cancer Res.
13, 6610-6616
|Abstract »|Full Text »|PDF »
Bcl-2 Orchestrates a Cross-talk between Endothelial and Tumor Cells that Promotes Tumor Growth.
T. Kaneko, Z. Zhang, M. G. Mantellini, E. Karl, B. Zeitlin, M. Verhaegen, M. S. Soengas, M. Lingen, R. M. Strieter, G. Nunez, et al. (2007)
Cancer Res.
67, 9685-9693
|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 »
Antiangiogenic Strategies on Defense: On the Possibility of Blocking Rebounds by the Tumor Vasculature after Chemotherapy.
Pharmacodynamic and pharmacokinetic study of chronic low-dose metronomic cyclophosphamide therapy in mice.
U. Emmenegger, Y. Shaked, S. Man, G. Bocci, I. Spasojevic, G. Francia, A. Kouri, R. Coke, W. Cruz-Munoz, S. M. Ludeman, et al. (2007)
Mol. Cancer Ther.
6, 2280-2289
|Abstract »|Full Text »|PDF »
Vascular Endothelial Growth Factor Trap Blocks Tumor Growth, Metastasis Formation, and Vascular Leakage in an Orthotopic Murine Renal Cell Cancer Model.
H. M.W. Verheul, H. Hammers, K. van Erp, Y. Wei, T. Sanni, B. Salumbides, D. Z. Qian, G. D. Yancopoulos, and R. Pili (2007)
Clin. Cancer Res.
13, 4201-4208
|Abstract »|Full Text »|PDF »
Molecular Basis of the Synergistic Antiangiogenic Activity of Bevacizumab and Mithramycin A.
Z. Jia, J. Zhang, D. Wei, L. Wang, P. Yuan, X. Le, Q. Li, J. Yao, and K. Xie (2007)
Cancer Res.
67, 4878-4885
|Abstract »|Full Text »|PDF »
An Orally Available Small-Molecule Inhibitor of c-Met, PF-2341066, Exhibits Cytoreductive Antitumor Efficacy through Antiproliferative and Antiangiogenic Mechanisms.
H. Y. Zou, Q. Li, J. H. Lee, M. E. Arango, S. R. McDonnell, S. Yamazaki, T. B. Koudriakova, G. Alton, J. J. Cui, P.-P. Kung, et al. (2007)
Cancer Res.
67, 4408-4417
|Abstract »|Full Text »|PDF »
Anticancer Therapies Combining Antiangiogenic and Tumor Cell Cytotoxic Effects Reduce the Tumor Stem-Like Cell Fraction in Glioma Xenograft Tumors.
C. Folkins, S. Man, P. Xu, Y. Shaked, D. J. Hicklin, and R. S. Kerbel (2007)
Cancer Res.
67, 3560-3564
|Abstract »|Full Text »|PDF »
Target Practice: Lessons from Phase III Trials with Bevacizumab and Vatalanib in the Treatment of Advanced Colorectal Cancer.
Functional Neoangiogenesis Imaging of Genetically Engineered Mouse Prostate Cancer Using Three-Dimensional Power Doppler Ultrasound.
J. W. Xuan, M. Bygrave, H. Jiang, F. Valiyeva, J. Dunmore-Buyze, D. W. Holdsworth, J. I. Izawa, G. Bauman, M. Moussa, S. F. Winter, et al. (2007)
Cancer Res.
67, 2830-2839
|Abstract »|Full Text »|PDF »
Mice expressing a humanized form of VEGF-A may provide insights into the safety and efficacy of anti-VEGF antibodies.
H.-P. Gerber, X. Wu, L. Yu, C. Wiesmann, X. H. Liang, C. V. Lee, G. Fuh, C. Olsson, L. Damico, D. Xie, et al. (2007)
PNAS
104, 3478-3483
|Abstract »|Full Text »|PDF »
Thrombospondin-1 Peptide ABT-510 Combined with Valproic Acid Is an Effective Antiangiogenesis Strategy in Neuroblastoma.
Q. Yang, Y. Tian, S. Liu, R. Zeine, A. Chlenski, H. R. Salwen, J. Henkin, and S. L. Cohn (2007)
Cancer Res.
67, 1716-1724
|Abstract »|Full Text »|PDF »
Alternative Vascularization Mechanisms in Cancer: Pathology and Therapeutic Implications.
B. Dome, M. J.C. Hendrix, S. Paku, J. Tovari, and J. Timar (2007)
Am. J. Pathol.
170, 1-15
|Abstract »|Full Text »|PDF »
