Genentech Oncology
1. What is the significance of VEGF (vascular endothelial growth factor) in tumor angiogenesis?
As demonstrated in preclinical models:
VEGF has been identified as a regulator of tumor angiogenesis.1
2. Why is VEGF essential throughout the tumor life cycle?
As demonstrated in preclinical models:
VEGF may play an essential role throughout the tumor cycle by helping tumor vessels establish, grow, and survive.2,3
3. What are the effects of VEGF inhibition?
Angiogenesis is a necessary part of the process in the progression of cancer from small, localized neoplasms to larger, growing, and potentially metastatic tumors. To grow beyond 1 to 2 mm in diameter, a tumor needs an independent blood supply, which is acquired by the expression of growth factors that recruit new vasculature from existing blood vessels (Figure 1). This process continues even as the tumor matures. Thus, upregulation of angiogenesis is a key step in sustained tumor growth and may also be critical for tumor metastasis.1,4
VEGF (also known as VEGF-A, but commonly referred to simply as VEGF) stands for "vascular endothelial growth factor." As its name suggests, VEGF stimulates vascular endothelial cell growth, survival, and proliferation.3,5
VEGF is a member of a family of 6 structurally related proteins (Table 1) that regulate the growth and differentiation of multiple components of the vascular system, especially blood and lymph vessels. The angiogenic effects of the VEGF family are thought to be primarily mediated through the interaction of VEGF with VEGFR-2.5-8
VEGF ligands |
Receptors |
Functions |
VEGF (VEGF-A) |
VEGFR-1, VEGFR-2, neuropilin-1 |
Angiogenesis |
VEGF-B |
VEGFR-1 |
Not established |
VEGF-C |
VEGFR-3 |
Lymphangiogenesis |
VEGF-D |
VEGFR-3 |
Lymphangiogenesis |
VEGF-E (viral factor) |
VEGFR-2 |
Angiogenesis |
Placental growth factor |
VEGFR-1, neuropilin-1 |
Angiogenesis |
VEGF ligands mediate their angiogenic effects by binding to specific VEGF receptors, leading to subsequent signal transduction.11
As the tumor develops, it may begin to activate secondary angiogenic pathways, such as basic fibroblast growth factor (bFGF), transforming growth factor beta (TGFβ), placental growth factor (PlGF), and platelet-derived endothelial cell growth factor (PD-ECGF). As these secondary pathways emerge, VEGF continues to be expressed and remains one of the critical mediators of angiogenesis (Figure 1).12
Expression of VEGF has been observed across a range of tumor types and has been widely correlated with tumor development and/or poor cancer prognosis.4,5,7
Targeting VEGF may result in ongoing inhibition of both new and recurrent tumor vessel growth (Table 1). It has been proposed that these effects may help inhibit tumor growth and metastasis.1,14
Research also suggests that blockade of VEGF signaling may help inhibit tumor growth by preventing new vessel growth at both primary and metastatic sites.1
Tumor vessel inhibition |
Tumor vessel regression |
Interferes with the ability of VEGF to help tumor vessels establish and grow Associated with reduced tumor growth and decreased metastatic potential |
Interferes with the ability of VEGF to help tumor vessels survive Associated with reduction in microvascular density and tumor volume |
Based on preclinical models, it has also been proposed that VEGF inhibition may regress existing tumor vessels (Table 1). These reductions in microvascular density have been associated with a reduction in tumor volume and weight (Figure 1).14,17
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Bautch VL. VEGF-directed blood vessel patterning: from cells to organism. Cold Spring Harb Perspect Med. 2012;2(9):a006452. doi:10.1101/cshperspect.a006452. PMID: 22951440
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Abhinand CS, Raju R, Soumya SJ, et al. VEGF-A/VEGFR2 signaling network in endothelial cells relevant to angiogenesis. J Cell Commun Signal. 2016;10(4):347-354. PMID: 27619687
Abhinand CS, Raju R, Soumya SJ, et al. VEGF-A/VEGFR2 signaling network in endothelial cells relevant to angiogenesis. J Cell Commun Signal. 2016;10(4):347-354. PMID: 27619687
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