Cellular and Molecular Life Sciences

, Volume 72, Issue 16, pp 3069–3082 | Cite as

Adaptation to antiangiogenic therapy in neurological tumors

  • Patrick M. Flanigan
  • Manish K. AghiEmail author


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.


Resistance Adaptive Glioblastoma Bevacizumab Pericytes Bone marrow Autophagy 



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


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Copyright information

© Springer Basel 2015

Authors and Affiliations

  1. 1.Cleveland Clinic Lerner College of MedicineClevelandUSA
  2. 2.Department of Neurological Surgery, California Center for Pituitary DisordersUniversity of CaliforniaSan FranciscoUSA

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