Chapter

Tumor Microenvironment and Cellular Stress

Volume 772 of the series Advances in Experimental Medicine and Biology pp 83-99

Date:

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

  • Lee RiveraAffiliated withDepartments of Neurological Surgery, University of California, Helen Diller Family Cancer Research CenterBrain Tumor Research Center, University of California, Helen Diller Family Cancer Research Center
  • , Melissa PandikaAffiliated withDepartments of Neurological Surgery, University of California, Helen Diller Family Cancer Research CenterBrain Tumor Research Center, University of California, Helen Diller Family Cancer Research Center
  • , Gabriele BergersAffiliated withDepartments of Neurological Surgery, University of California, Helen Diller Family Cancer Research CenterBrain Tumor Research Center, University of California, Helen Diller Family Cancer Research CenterAnatomy, University of California, Helen Diller Family Cancer Research CenterUCSF Comprehensive Cancer Center, University of California, Helen Diller Family Cancer Research Center Email author 

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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.

Keywords

Cancer Antiangiogenic therapy Resistance Innate immune cells Macrophages Myeloid-derived suppressor cells (MDSCs) Neovascularization