VEGF signaling: Role in angiogenesis and beyond

Area of Science:

• Oncology
• Molecular Biology
• Cell Biology

Background:

• Angiogenesis, driven by vascular endothelial growth factor (VEGF), is vital for tumor growth and survival.
• VEGF's established role in neovascularization is critical, but its broader influence on the tumor microenvironment is less understood.

Purpose of the Study:

• To review the multifaceted roles of VEGF beyond angiogenesis within the tumor microenvironment.
• To explore VEGF's impact on intercellular communications, including pericyte and immune cell interactions.
• To discuss VEGF's involvement in tumor metabolism, stemness, and epithelial-mesenchymal transition (EMT).

Main Methods:

• Comprehensive literature review of studies investigating VEGF signaling in cancer.
• Analysis of VEGF's effects on cellular processes such as proliferation, migration, and intercellular crosstalk.
• Evaluation of current anti-VEGF therapies and their clinical limitations.

Main Results:

• VEGF significantly influences pericyte behavior and mediates interactions between tumor-associated macrophages and cancer cells, leading to immunosuppression (PD-L1) and EMT (Nrf2).
• VEGF signaling is implicated in intra-organelle crosstalk, tumor metabolism, cancer stemness, and EMT.
• Current anti-VEGF therapies face limitations in overcoming tumor resistance and heterogeneity.

Conclusions:

• VEGF is a critical regulator of multiple oncogenic processes, extending beyond its role in angiogenesis.
• Understanding VEGF's comprehensive impact on the tumor microenvironment is essential for developing more effective cancer therapies.
• Targeting VEGF and its downstream pathways offers potential for improved cancer treatment strategies.