Hypoxia, Tumor Endothelium, and Targets for Therapy

  • Beverly A. Teicher
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 566)


Hypoxia is a well-recognized feature of human solid tumors. It is also well recognized, by both physicians and investigators, that malignant disease in various organs/tissues in the same patient, or the same tumor cells implanted in different sites or organs in the preclinical host, have different levels of hypoxia and different levels of response to systemic therapies. Over the past 10 years, it has been established that normal cells involved in the malignant disease process can be important targets for therapeutic attack. A prime example of ‘normal’ cells that have come to the fore as anticancer therapeutic targets is endothelial cells.

The field of antiangiogenic therapies was fueled by the early hypothesis which held that angiogenesis was the same no matter where it occurred. The corollary to this hypothesis was that models of normal embryo development, as well as models working with mature well-differentiated endothelial cells in culture, would be sufficient and satisfactory models for tumor endothelial cells. However, the current hypothesis is that angiogenesis occurring during malignant disease is abnormal, and that therapeutic targets identified by studying endothelial cells isolated from fresh samples of human cancers will be most relevant in developing therapeutic agents to treat human malignant disease.


Antiangiogenic Therapy Human Tumor Xenograft Tumor Endothelial Cell Matrigel Plug Endothelial Precursor Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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4. References

  1. 1.
    C. M. Doll, M. Milosevic, M. Pintilie, R. P. Hill, and A. W. Fyles, Estimating hypoxic status in human tumors: A simulation using Eppendorf oxygen probe data in cervical cancer patients, Int. J. Radiat. Oncol. Biol. Phys. 55(5), 1239–1246 (2003).PubMedCrossRefGoogle Scholar
  2. 2.
    A. Fyles, M. Milosevic, D. Hedley, M. Pintilie, W. Levin, L. Manchul, and R. P. Hill, Tumor hypoxia has independent predictor impact only in patients with node-negative cervix cancer, J. Clin. Oncol. 20(3), 680–687 (2002).PubMedCrossRefGoogle Scholar
  3. 3.
    J.-Y. Wang, K.-Y. Chen, J.-T. Wang, J.-H. Chen, J.-W. Lin, H.-C. Wang, L.-N. Lee, and P.-C. Yang, Outcome and prognostic factors for patients with non-small cell lung cancer and severe radiation pneumonitis, Int. J. Radiat. Oncol. Biol. Phys. 54(3), 735–741 (2002).PubMedCrossRefGoogle Scholar
  4. 4.
    J. Dunst, T. Kuhnt, H. G. Strauss, U. Krause, T. Pelz, H. Koelbl, and G. Haensgen, Anemia in cervical cancers: impact on survival, patterns of relapse, and association with hypoxia and angiogenesis, Int. J. Radiat. Oncol. Biol. Phys. 56(3), 778–787 (2003).PubMedCrossRefGoogle Scholar
  5. 5.
    B. Movsas, J. D. Chapman, A. L. Hanlon, E. M. Horwitz, W. H. Pinover, R. E. Greenberg, C. Stobbe, and G. E. Hanks, Hypoxia in human prostate carcinoma: An Eppendorf PO2 study, Am. J. Clin. Oncol. 24(5), 458–461 (2001).PubMedCrossRefGoogle Scholar
  6. 6.
    P. Subarsky, and R. P. Hill, The hypoxic tumor microenvironment and metastatic progression, Clin. Exp. Metastasis 20, 237–250 (2003).PubMedCrossRefGoogle Scholar
  7. 7.
    S. A. Holden, Y. Emi, Y. Kakeji, D. Northey, and B. A. Teicher, Host distribution and response to antitumor alkylating agents of EMT-6 tumor cells from subcutaneous tumor implants, Cancer Chemother. Pharmacol. 40, 87–93 (1997).PubMedCrossRefGoogle Scholar
  8. 8.
    B. A. Teicher, G. Ara, S. R. Keyes, R. S. Herbst, and E. Frei III, Acute in vivo resistance in high-dose therapy, Clin. Cancer Res. 4, 483–491 (1998).PubMedGoogle Scholar
  9. 9.
    B. St. Croix, C. Rago, V. Velculescu, G. Traverso, K. E. Romans, E. Montgomery, A. Lai, G. J. Riggins, C. Lengauer, B. Vogelstein, and K. W. Kinzler, Genes expressed in human tumor endothelium, Science 289(5482), 1197–1202 (2000).PubMedCrossRefGoogle Scholar
  10. 10.
    R. G. Bagley, J. Walter-Yohrling, X. Cao, W. Weber, B. Simons, B. P. Cook, S. D. Chartrand, C. Wang, S. L. Madden, and B. A. Teicher, Endothelial precursor cells as a model of tumor endothelium: characterization and comparison with mature endothelial cells, Cancer Res. 63(18), 5866–5873 (2003).PubMedGoogle Scholar
  11. 11.
    Y. Kakeji, and B. A. Teicher, Preclinical studies of the combination of angiogenic inhibitors with cytotoxic agents, Invest. New Drugs 15, 39–48 (1997).PubMedCrossRefGoogle Scholar
  12. 12.
    K. A. Keyes, L. Mann, K. Cox, P. Treadway, P. Iversen, Y.-F. Chen, and B. A. Teicher, Circulating angiogenic growth factor levels in mice bearing human tumors using Luminex multiplex technology, Cancer Chemother. Pharmacol. 51, 321–327 (2003).PubMedGoogle Scholar
  13. 13.
    K. Keyes, K. Cox, P. Treadway, L. Mann, C. Shih, M. M. Faul, and B. A. Teicher, An in vitro tumor model: analysis of angiogenic factor expression after chemotherapy, Cancer Res. 62, 5597–5602 (2002).PubMedGoogle Scholar
  14. 14.
    B. A. Teicher, K. Menon, E. Alvarez, E. Galbreath, C. Shih, and M. M. Faul, Antiangiogenic and antitumor effects of a protein Kinase Cb inhibitor in human T98G glioblastoma multiforme xenografts, Clin. Cancer Res. 7, 634–640 (2001).PubMedGoogle Scholar
  15. 15.
    K. A. Keyes, L. Mann, M. Sherman, E. Galbreath, L. Schirtzinger, D. Ballard, Y.-F. Chen, P. Iversen, and B. A. Teicher, LY317615 decreases plasma VEGF levels in human tumor xenograft bearing mice, Cancer Chemother. Pharmacol. 53(2), 133–140(2003).Google Scholar

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© Springer Science+Business Media, Inc. 2005

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  • Beverly A. Teicher

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