VEGF in tumor progression and targeted therapy

Area of Science:

• Oncology
• Cancer Biology
• Translational Medicine

Background:

• Tumor progression relies on vascularization and angiogenesis, with vascular endothelial growth factor A (VEGF-A) being a key proangiogenic factor.
• VEGF-A blockade, exemplified by bevacizumab, is used in treating various cancers, including breast and colorectal cancers, and recurrent high-grade gliomas (HGGs).
• While bevacizumab can improve progression-free survival and quality of life, its efficacy in brain tumors like HGGs is debated due to limited recovery and potential for enhanced invasion.

Purpose of the Study:

• To evaluate the role of anti-VEGF therapy in solid tumor progression, particularly in high-grade gliomas (HGGs).
• To explore the challenges and resistance mechanisms associated with anti-VEGF therapy in HGGs.
• To propose multi-target strategies for enhancing antitumor treatment efficacy beyond VEGF-A inhibition.

Main Methods:

• Review of existing clinical practices and research on anti-VEGF therapies, including bevacizumab.
• Analysis of mechanisms of resistance to anti-VEGF therapy in HGGs.
• Discussion of alternative and complementary therapeutic strategies.

Main Results:

• Anti-VEGF therapy can inhibit tumor vascularization and growth but shows controversial efficacy in HGGs, offering only modest delay and not complete recovery.
• Resistance mechanisms include alternative proangiogenic pathways, invasive tumor cell populations, metabolic shifts to glycolysis, and recruitment of myeloid cells.
• Anti-VEGF antibodies show potential as drug delivery vectors for brain tumors.

Conclusions:

• Anti-VEGF therapy as monotherapy is insufficient for HGGs.
• A multi-target strategy is essential to inhibit angiogenesis, invasion, autophagy, metastasis, and the recruitment of specific cell types.
• Anti-VEGF antibodies may serve as valuable vectors for targeted drug and diagnostic delivery in brain tumors.