<b>Background:</b> Overexpression of VEGF is implicated in the pathogenesis of both renal cell carcinoma (RCC) and age-related macular degeneration (AMD).
5-LO was frequently overexpressed in von Hippel-Lindau protein (pVHL)-reduced tumors and in Vascular Endothelial Growth Factor (VEGF)-positive tumors, which represent two frequent alterations in CC-RCC.
Renal cell carcinoma is characterized by the frequent loss of the von Hippel-Lindau tumor suppressor gene which results in the loss of one of the critical mechanisms for regulating the level of hypoxia inducible factor 1 and leads to the overproduction of vascular endothelial growth factor (VEGF) by the tumor cell.
Renal cell carcinoma (RCC) is a metabolic disease, being characterized by the dysregulation of metabolic pathways involved in oxygen sensing (VHL/HIF pathway alterations and the subsequent up-regulation of HIF-responsive genes such as VEGF, PDGF, EGF, and glucose transporters GLUT1 and GLUT4, which justify the RCC reliance on aerobic glycolysis), energy sensing (fumarate hydratase-deficient, succinate dehydrogenase-deficient RCC, mutations of HGF/MET pathway resulting in the metabolic Warburg shift marked by RCC increased dependence on aerobic glycolysis and the pentose phosphate shunt, augmented lipogenesis, and reduced AMPK and Krebs cycle activity) and/or nutrient sensing cascade (deregulation of AMPK-TSC1/2-mTOR and PI3K-Akt-mTOR pathways).
RCC is a particularly vascular tumor that has been demonstrated to lead to the abnormal expression of various angiogenesis-promoting growth factors, including vascular endothelial growth factor.
Vascular endothelial growth factor and mammalian target of rapamycin-targeted therapies continue to play a critical role in the management of advanced and metastatic RCC.
VEGF plays an important role in the occurrence and development of RCC, chemical synthesis of VEGF small interfering RNA (siRNA) can specifically inhibit VEGF expression, angiogenesis and growth in RCC, and can promote cell apoptosis without genetic toxicity to normal tissues.
VEGF has prognostic value in clear cell renal cell carcinoma, and ERK5 may be a new prognostic marker in this type of tumor owing to its relationship with metastasis and more advanced stages.
A middle-aged man with conventional clear cell renal cell carcinoma (RCC) had received multiple prior systemic treatments including vascular endothelial growth factor receptor tyrosine kinase inhibitors, as well as multiple surgeries and radiotherapy treatments.
A number of treatments targeting VEGF or mTOR pathways have been approved for metastatic clear cell Renal Cell Carcinoma (ccRCC), but the majority of patients show disease progression after first line therapy with a very low rate of complete or long-term responders.
A prospective, longitudinal cohort study was conducted with 50 patients diagnosed with clear-cell renal cell carcinoma to analyze VHL mutations and hypermethylation as well as VHL, HIF1-α, vascular endothelial growth factor (VEGF), ERK1/2, and ERK5 protein expression.
A significant early discovery in RCC was frequent inactivation of the Von Hippel Lindau gene in ccRCC, which ultimately led to the development of vascular endothelial growth factor and mammalian target of rapamycin inhibitors.
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.
Adjuvant treatment of renal cell carcinoma with vascular endothelial growth factor inhibitors is feasible and effective with careful patient selection and standard dosing levels.
Adjuvant treatment with vascular endothelial growth factor receptor tyrosine kinase inhibitor in renal cell carcinoma after nephrectomy has been reported through three clinical trials: S-TRAC, ASSURE and PROTECT.