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Adaptation to antiangiogenic therapy in neurological tumors

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Abstract

Because tumors require a vascular supply for their survival and growth, angiogenesis is considered an important therapeutic target in most human cancers including cancer of the central nervous system. Antiangiogenic therapy has focused on inhibitors of the vascular endothelial growth factor (VEGF) signaling pathway. VEGF pathway-targeted drugs have shown therapeutic efficacy in several CNS tumors and have been tried most frequently in glioblastoma. These therapies, however, have been less effective than anticipated as some patients do not respond to therapy and some receive only modest benefit. Underlying this suboptimal response are multiple mechanisms of drug resistance involving changes in both tumor cells and their microenvironment. In this review, we discuss the multiple proposed mechanisms by which neurological tumors evolve to become resistant to antiangiogenic therapies. A better understanding of these mechanisms, their context, and their interplay will likely facilitate improvements in pharmacological strategies for the targeted treatment of neurological tumors.

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Acknowledgments

This work was supported by funding to M.K.A.’s laboratory from the NIH (1 R01 NS079697).

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Authors and Affiliations

  1. Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA

    Patrick M. Flanigan

  2. Department of Neurological Surgery, California Center for Pituitary Disorders, University of California, San Francisco, USA

    Manish K. Aghi

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Correspondence to Manish K. Aghi.

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Flanigan, P.M., Aghi, M.K. Adaptation to antiangiogenic therapy in neurological tumors. Cell. Mol. Life Sci. 72, 3069–3082 (2015). https://doi.org/10.1007/s00018-015-1916-0

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  • DOI: https://doi.org/10.1007/s00018-015-1916-0

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