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Tumor Microenvironment and Cellular Stress pp 83–99Cite as

Escape Mechanisms from Antiangiogenic Therapy: An Immune Cell’s Perspective

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 772))

Abstract

Neovascularization, the formation of new blood vessels, has become a well-established hallmark of cancer. Its functional importance for the manifestation and progression of tumors has been validated further by the beneficial therapeutic effects of angiogenesis inhibitors, most notably those targeting vascular endothelial growth factor signaling pathways. However, with the transient and short-lived nature of patient response, it has become evident that tumors have the ability to adapt to the pressures of vascular growth restriction. Observations made both in the clinic and at the bench suggest the existence of several escape mechanisms that either reestablish neovascularization in tumors or change tumor behavior to enable propagation and progression without obligate neovascularization. Some of these bypass mechanisms are regulated by low oxygen conditions (hypoxia) caused by therapy-induced vessel regression. Induction of hypoxia and hypoxia-inducible factors regulate a wide range of tumor-promoting pathways, including those of neovascularization, that can upregulate additional proangiogenic factors and drive the recruitment of various bone marrow–derived cells that have the capacity to express proangiogenic factors or directly contribute to neovasculature.

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Authors and Affiliations

  1. Departments of Neurological Surgery, University of California, Helen Diller Family Cancer Research Center, 1450 3rd Street, MC 0520, San Francisco, CA, 94158-9001, USA

    Lee Rivera, Melissa Pandika & Gabriele Bergers Ph.D.

  2. Brain Tumor Research Center, University of California, Helen Diller Family Cancer Research Center, San Francisco, CA, 94158, USA

    Lee Rivera, Melissa Pandika & Gabriele Bergers Ph.D.

  3. Anatomy, University of California, Helen Diller Family Cancer Research Center, San Francisco, CA, 94158, USA

    Gabriele Bergers Ph.D.

  4. UCSF Comprehensive Cancer Center, University of California, Helen Diller Family Cancer Research Center, 1450 3rd Street, MC 0520, San Francisco, CA, 94158-9001, USA

    Gabriele Bergers Ph.D.

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  1. Lee Rivera
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  2. Melissa Pandika
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  3. Gabriele Bergers Ph.D.
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Correspondence to Gabriele Bergers Ph.D. .

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Editors and Affiliations

  1. Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA

    Constantinos Koumenis

  2. Cancer Research, Gray Institute for Radiation Oncology, Oxford, United Kingdom

    Ester Hammond

  3. Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California, USA

    Amato Giaccia

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Rivera, L., Pandika, M., Bergers, G. (2014). Escape Mechanisms from Antiangiogenic Therapy: An Immune Cell’s Perspective. In: Koumenis, C., Hammond, E., Giaccia, A. (eds) Tumor Microenvironment and Cellular Stress. Advances in Experimental Medicine and Biology, vol 772. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5915-6_4

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