To examine the combined findings of all three VEGFR
TKI-based adjuvant studies including the most recent PROTECT trial, we performed a meta-analysis of the S-TRAC, ASSURE and PROTECT results using DFS and OS data from their original reports.[1-3] Median DFS estimates for sunitinib vs.
VEGF/VEGFR axis can be therapeutically targeted either with antibodies aimed at the soluble extracellular ligands or with small molecule inhibitors (tyrosine kinase inhibitors, TKIs) which block the intracellular domains of VEGFRs
. Bevacizumab, a humanized monoclonal antibody against VEGF-A is approved for use in combination with chemotherapy in patients with metastatic colorectal cancer and ovarian cancer [8, 9].
In the dog in this report, the expression of VEGFr
, PDGFr, EGFr, and SCF was demonstrated by immunohistochemistry.
The underlying mechanism may be due to the complex interaction of VEGFs and VEGFRs
. Ranibizumab and bevacizumab are antibodies that target VEGF-A.
The main mechanism of action is mediated by effective blocking of vascular endothelial growth factor receptors (VEGFRs
) 1-3, platelet-derived growth factor receptor-[alpha] (PDGFR-[alpha]) and PDGFR-[beta], and c-Kit .
Western blot confirmed that there was no significant difference in VEGFR
in colon tissue homogenates among the low- and moderate-dose Garidisan, SASP, and Bupiyichangwan groups and normal controls.
Sulfatinib is an oral drug candidate that selectively inhibits the tyrosine kinase activity associated with the vascular endothelial growth factor receptor (VEGFR
) and fibroblast growth receptor (FGFR), two tyrosine kinase receptors associated with angiogenesis and tumor growth.
In contrast, abdominal fur does not regrow properly in rats that have been treated with AEE788, a dual inhibitor of epidermal growth factor receptor (EGFR) and VEGFR
, over 4 weeks (Deng et al., 2011).
Its receptor VEGFR
is involved in both vasculogenesis and angiogenesis (see Figure 4).
These families include VEGF receptor (VEGFR
) types 1 (FLT1), 2 (KDR), and 3 (FLT4); platelet-derived growth factor receptors A and B (PDGFRA and PDGFRB); the stem cell factor receptor (cKIT); FMS-like tyrosine kinase 3 (FLT3); colony-stimulating factor 1 receptor (CSF-1R); and glial cell line-derived neurotrophic factor receptor [rearranged during transfection (RET)].
Therapeutic approaches target the VEGF ligand (bevacizumab (anti-VEGF monoclonal antibody), aflibercept (VEGF Trap)) or the tyrosine kinase receptor [sunitinib, sorafenib, and pazopanib] TKI interfere with the activity of VEGFR
and other growth factors, among them PDGF receptors (PDGFRs), stem cell factor receptor (c-kit), FMS-like tyrosine kinase-3 (Flt-3), and b-raf and Bcl-Abl.
It has been shown that VEGF-A induces proliferation, survival, and protection of AML cells against apoptosis by an autocrine loop via VEGFR
signaling (31), (32), (33).