Single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor receptor (VEGFR) may have effects on the MAPK/ERK/STAT3 signaling pathway, and the resulting phenotypes may influence the response to sunitinib-targeted therapy for renal cell carcinoma.
<b>Background:</b> Overexpression of VEGF is implicated in the pathogenesis of both renal cell carcinoma (RCC) and age-related macular degeneration (AMD).
MicroRNA-185 inhibits cell proliferation and induces cell apoptosis by targeting VEGFA directly in von Hippel-Lindau-inactivated clear cell renal cell carcinoma.
Currently, four VEGF receptor inhibitors (sorafenib, sunitinib, pazopanib and axitinib), one anti-VEGF monoclonal antibody (bevacizumab) and two inhibitors of the mTOR pathway (temsirolimus and everolimus) have been approved to treat renal cell carcinoma (RCC), and several other molecules are under investigation.
In the current study, the authors investigated the effect of vascular endothelial growth factor (VEGF)-targeted therapy in this distinct subtype of RCC.
In a randomized, placebo-controlled, double-blind trial, we tested the use of a neutralizing antibody to vascular endothelial growth factor, bevacizumab, in patients with metastatic RCC.
Here, we describe a novel pathway whereby Sp1 promotes the transcription of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF), a potent angiogenic factor, by interacting directly and specifically with protein kinase C zeta (PKC zeta) isoform in renal cell carcinoma.
Recently, ramucirumab, a drug that targets vascular endothelial growth factor receptor (VEGFR), was clinically approved; therefore, we evaluated VEGFR2 expression and its predictive roles in tumor progression in clear cell renal cell carcinoma (CCRCC).
Additionally, THZ1 reduced VEGF expression in human RCC cells (786-O and Caki-2), and THZ1 treatment inhibited tumor growth, vascularity, and angiogenic marker (CD31) expression in RCC xenografts.
Since HIF regulates critical angiogenic factors such as vascular endothelial growth factor (VEGF) and lesions in VHL gene are present in a majority of the highly vascularized renal cell carcinoma (RCC), it is believed that deregulation of the VHL-HIF pathway is crucial for the proangiogenic activity of RCC.
This study evaluated the association of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) genetic polymorphisms with the development of hypertension (HTN) and clinical outcome in metastatic clear cell renal cell carcinoma (MCCRCC) patients treated with sunitinib.
Moreover, our data illustrated that phosphoinositide 3-kinase/AKT signaling pathway is involved in Rap2B-mediated upregulation of vascular endothelial growth factor and renal cell carcinoma angiogenesis.
Over the past decade, therapies targeting the VEGF/VEGFR and mTOR pathways have served as the standard of care for the clinical management of renal cell carcinoma (RCC) patients.
Moreover, preliminary data indicate that HIF plays a critical role in pVHL-defective tumor formation, raising the possibility that drugs directed against HIF or its downstream targets (such as vascular endothelial growth factor) might one day play a role in the treatment of hemangioblastoma and renal cell carcinoma.
Most cases of sporadic as well as familial ccRCC acquire somatic inactivating mutations of the von Hippel-Lindau tumor-suppressor gene, VHL. pVHL, VHL gene product and a protein member of the E3 ubiquitin ligase family, acts in normal cells to direct the degradation and clearance of the hypoxia inducible factor (HIF)alpha transcription factor family, such that in its absence, as in ccRCC, the HIF proteins stabilize, accumulate to supraphysiologic levels and activate the transcription of genes such as VEGF and PDGF, which contributes substantially to the physiology of the tumor, and has been assessed indirectly as a prognostic factor.
Kinase inhibitors targeting vascular endothelial growth factor receptors (VEGFR) and mammalian target of rapamycin (mTOR) improve outcomes in metastatic clear cell renal cell carcinoma (ccRCC), but are not curative.
Targeted therapy against VEGF and mTOR pathways has been established as the standard-of-care for metastatic clear cell renal cell carcinoma (ccRCC); however, these treatments frequently fail and most patients become refractory requiring subsequent alternative therapeutic options.
The treatment options for advanced RCC are rapidly evolving since the introduction of VEGF-targeted therapy, immunotherapy with checkpoint blockade and, more recently, combination regimens.
We aimed to perform a comparative analysis of tumor cells and blood vessels from renal cell carcinoma on endostatin-treated and non-treated chorioallantoic membrane (CAM) implants by the assessment of endoglin, vascular endothelial growth factor (VEGF) and smooth muscle actin expression.