Old Player-New Tricks: Non Angiogenic Effects of the VEGF/VEGFR Pathway in Cancer

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Angiogenesis, driven by the vascular endothelial growth factor/receptor (VEGF/VEGFR) pathway, is crucial for cancer growth.
• Anti-angiogenic therapies targeting VEGF/VEGFR have shown moderate success, primarily focusing on endothelial cells.
• Emerging evidence highlights VEGF's broader roles in tumor cell survival, proliferation, invasion, and immune suppression.

Purpose of the Study:

• To review the multifaceted effects of the VEGF/VEGFR pathway on non-endothelial cells, including tumor and immune cells.
• To explore the implications of anti-angiogenic agents beyond their direct impact on blood vessels.
• To present the scientific rationale for combining anti-angiogenic therapies with immunotherapies.

Main Methods:

• Literature review of studies investigating VEGF/VEGFR signaling in cancer.
• Analysis of research on the effects of VEGF on tumor cells and the tumor microenvironment.
• Synthesis of findings related to anti-angiogenic agents' impact on non-endothelial targets.

Main Results:

• VEGF/VEGFR signaling directly influences tumor cell proliferation, invasion, and survival.
• VEGF contributes to an immunosuppressive tumor microenvironment.
• Disruption of VEGF/VEGFR exhibits immunostimulatory functions and promotes tumor regression.

Conclusions:

• The VEGF/VEGFR pathway has significant non-endothelial functions relevant to cancer progression and immune evasion.
• Anti-angiogenic agents offer direct anti-tumor effects and immunomodulatory benefits.
• Combining anti-angiogenic therapies with immunotherapy presents a promising strategy for enhanced cancer treatment.