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Adaptation to antiangiogenic therapy in neurological tumors
Patrick M Flanigan1, Manish K Aghi
1Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA.
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.
Insights
Antiangiogenic therapies targeting vascular endothelial growth factor (VEGF) show limited success in brain tumors due to resistance. Understanding resistance mechanisms is key to improving these cancer treatments.
Area of Science:
- Oncology
- Neuro-oncology
- Cancer Biology
Background:
- Tumor growth and survival depend on angiogenesis, making it a key therapeutic target in cancers, including central nervous system (CNS) tumors.
- Antiangiogenic therapies, primarily targeting the vascular endothelial growth factor (VEGF) signaling pathway, have been investigated for CNS tumors, particularly glioblastoma.
Purpose of the Study:
- To review and discuss the proposed mechanisms of drug resistance in neurological tumors against antiangiogenic therapies.
- To highlight the need for a deeper understanding of resistance mechanisms to improve therapeutic strategies.
Main Methods:
- Literature review of studies on antiangiogenic therapy resistance in neurological tumors.
- Analysis of proposed mechanisms involving tumor cells and their microenvironment.
Main Results:
- Antiangiogenic therapies, while showing some efficacy, have suboptimal responses in many patients due to drug resistance.
- Multiple mechanisms contribute to resistance, involving alterations in both tumor cells and the tumor microenvironment.
Conclusions:
- Resistance to antiangiogenic therapies in neurological tumors is complex and multifactorial.
- Further understanding of these resistance mechanisms and their interplay is crucial for developing more effective targeted treatment strategies.
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