© 2002 by Oxford University Press
Journal of the National Cancer Institute, Vol. 94, No. 12, 883-893,
June 19, 2002
© 2002 Oxford University Press
REVIEW |
Clinical Application of Antiangiogenic Therapy: Microvessel Density, What It Does and Doesn't Tell Us
Affiliations of authors: L. Hlatky, P. Hahnfeldt, Dana-Farber Cancer Institute and the Department of Radiation Oncology, Harvard Medical School, Boston, MA; J. Folkman, Laboratory of Surgical Research, Department of Surgery, Children's Hospital, Boston, and Departments of Cell Biology and Surgery, Harvard Medical School.
Correspondence to: Lynn Hlatky, Ph.D., JFB-523, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney St., Boston, MA 02115 (e-mail: Lynn_Hlatky@dfci.harvard.edu).
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INTRODUCTION |
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A substantial number of clinical trials using antiangiogenic therapies are ongoing worldwide. How to achieve the maximum benefit from these therapies and how to monitor patient response are of paramount concern to investigators. There are currently no markers of the net angiogenic activity of a tumor available to aid investigators in the design of antiangiogenic treatment schemes. It stands to reason that quantification of various aspects of tumor vasculature might provide an indication of angiogenic activity. One often-quantified aspect of tumor vasculature is microvessel density. Studies over the last decade have demonstrated the value of using tumor microvessel density as a prognostic indicator for a wide range of cancers. In this context, measurement of microvessel density facilitates assessments of disease stage and the likelihood of recurrence and helps guide treatment decisions. Recently, however, it has been assumed by some investigators that measurements of microvessel density may also reveal the degree
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MICROVESSEL DENSITY IS A USEFUL PROGNOSTIC INDICATOR |
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MICROVESSEL DENSITY MAY NOT BE AN INDICATOR OF ANTIANGIOGENIC TREATMENT EFFICACY |
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1) Microvessel Density Is Not a Measure of the Angiogenic Dependence of a Tumor. To a Large Degree, It Reflects the Metabolic Burden of the Supported Tumor Cells.
2) The Measurement of Microvessel Density Is Not Predictive of Tumor Response Under Antiangiogenic Treatment and Therefore Is Not Useful for Stratifying Patients for Clinical Trials. Low Microvessel Density Does Not Portend a Poor Response to Antiangiogenic Therapy.
3) Tumor Microvessel Density May Not Vary in Accordance With the Tissue or Blood Levels of any Single Proangiogenic Factor.
4) A Minimum Vessel Density Is Determined by Tumor Cell Metabolic Demand, but Vessel Density Can Exceed the Metabolic Requirements of a Tumor.
5) Rapid Tumor Growth Does Not Imply High Vascular Density. The Microvessel Density of a Tumor Need Not Be Higher, and Is Often Lower, Than That of its Corresponding Normal Tissue, Which Is Experiencing no Net Growth.
6) The Efficacy of Antiangiogenic Agents Cannot Be Simply Visualized by Alterations in Microvessel Density During Treatment.
7) All Tumor Microvessels Are Not Functionally Equal. Inhibition of Ineffective Vessels Has Little Consequence in the Reduction of Tumor Growth, Further Emphasizing the Lack of a Simple Quantitative Relationship Between Alterations in Microvessel Density and Tumor Inhibition During Antiangiogenic Treatment.
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LOOKING BEYOND MEASUREMENTS OF MICROVESSEL DENSITY |
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NOTES |
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G. Petrangolini, G. Pratesi, M. De Cesare, R. Supino, C. Pisano, M. Marcellini, V. Giordano, D. Laccabue, C. Lanzi, and F. Zunino Antiangiogenic Effects of the Novel Camptothecin ST1481 (Gimatecan) in Human Tumor Xenografts Mol. Cancer Res., October 1, 2003; 1(12): 863 - 870. [Abstract] [Full Text] [PDF]
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M. D. Wheeler, O. M. Smutney, and R. J. Samulski Secretion of Extracellular Superoxide Dismutase From Muscle Transduced With Recombinant Adenovirus Inhibits the Growth of B16 Melanomas in Mice Mol. Cancer Res., October 1, 2003; 1(12): 871 - 881. [Abstract] [Full Text] [PDF]
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F. Denis, S. Colas, L. Chami, P. Louisot, O. le Floch, F. Tranquart, and P. Bougnoux Changes in Tumor Vascularization after Irradiation, Anthracyclin, or Antiangiogenic Treatment in Nitrosomethyl Ureas-Induced Rat Mammary Tumors Clin. Cancer Res., October 1, 2003; 9(12): 4546 - 4552. [Abstract] [Full Text] [PDF]
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P. M. Winter, S. D. Caruthers, A. Kassner, T. D. Harris, L. K. Chinen, J. S. Allen, E. K. Lacy, H. Zhang, J. D. Robertson, S. A. Wickline, et al. Molecular Imaging of Angiogenesis in Nascent Vx-2 Rabbit Tumors Using a Novel {alpha}{nu}{beta}3-targeted Nanoparticle and 1.5 Tesla Magnetic Resonance Imaging Cancer Res., September 15, 2003; 63(18): 5838 - 5843. [Abstract] [Full Text] [PDF]
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 F. Denis, P. Bougnoux, L. Paon, O. le Floch, and F. Tranquart Radiosensitivity of Rat Mammary Tumors Correlates With Early Vessel Changes Assessed by Power Doppler Sonography J. Ultrasound Med., September 1, 2003; 22(9): 921 - 929. [Abstract] [Full Text] [PDF]
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R. Giavazzi, B. Sennino, D. Coltrini, A. Garofalo, R. Dossi, R. Ronca, M. P. M. Tosatti, and M. Presta Distinct Role of Fibroblast Growth Factor-2 and Vascular Endothelial Growth Factor on Tumor Growth and Angiogenesis Am. J. Pathol., June 1, 2003; 162(6): 1913 - 1926. [Abstract] [Full Text] [PDF]
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H. Morioka, L. Weissbach, T. Vogel, G. P. Nielsen, G. T. Faircloth, L. Shao, and F. J. Hornicek Antiangiogenesis Treatment Combined with Chemotherapy Produces Chondrosarcoma Necrosis Clin. Cancer Res., March 1, 2003; 9(3): 1211 - 1217. [Abstract] [Full Text] [PDF]
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O. Straume, P. O. Chappuis, H. B. Salvesen, O. J. Halvorsen, S. A. Haukaas, J. R. Goffin, L. R. Begin, W. D. Foulkes, and L. A. Akslen Prognostic Importance of Glomeruloid Microvascular Proliferation Indicates an Aggressive Angiogenic Phenotype in Human Cancers Cancer Res., December 1, 2002; 62(23): 6808 - 6811. [Abstract] [Full Text] [PDF]
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