Exploring the Past, Present, and Future of Anti-Angiogenic Therapy in Glioblastoma
Author:
Zhang Ashley B.12ORCID, Mozaffari Khashayar1, Aguirre Brian3, Li Victor3, Kubba Rohan3, Desai Nilay C.3, Wei Darren3ORCID, Yang Isaac1ORCID, Wadehra Madhuri3ORCID
Affiliation:
1. Department of Neurosurgery, University of California, Los Angeles, CA 90095, USA 2. Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA 3. Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA
Abstract
Glioblastoma, a WHO grade IV astrocytoma, constitutes approximately half of malignant tumors of the central nervous system. Despite technological advancements and aggressive multimodal treatment, prognosis remains dismal. The highly vascularized nature of glioblastoma enables the tumor cells to grow and invade the surrounding tissue, and vascular endothelial growth factor-A (VEGF-A) is a critical mediator of this process. Therefore, over the past decade, angiogenesis, and more specifically, the VEGF signaling pathway, has emerged as a therapeutic target for glioblastoma therapy. This led to the FDA approval of bevacizumab, a monoclonal antibody designed against VEGF-A, for treatment of recurrent glioblastoma. Despite the promising preclinical data and its theoretical effectiveness, bevacizumab has failed to improve patients’ overall survival. Furthermore, several other anti-angiogenic agents that target the VEGF signaling pathway have also not demonstrated survival improvement. This suggests the presence of other compensatory angiogenic signaling pathways that surpass the anti-angiogenic effects of these agents and facilitate vascularization despite ongoing VEGF signaling inhibition. Herein, we review the current state of anti-angiogenic agents, discuss potential mechanisms of anti-angiogenic resistance, and suggest potential avenues to increase the efficacy of this therapeutic approach.
Subject
Cancer Research,Oncology
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