Renal cell carcinoma (RCC) is highly dependent on angiogenesis, due to the overactivation of the VHL/HIF/VEGF/VEGFRs axis; this justifies the marked sensitivity of this neoplasm to antiangiogenic agents which, however, ultimately fail to control tumor growth.
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.
658 patients with advanced RCC who had received at least one prior VEGFR tyrosine kinase inhibitor were randomised 1:1 to cabozantinib (60 mg daily) or everolimus (10 mg daily).
Addressing the best treatment for non-clear cell renal cell carcinoma: A meta-analysis of randomised clinical trials comparing VEGFR-TKis versus mTORi-targeted therapies.
The inverse association of angiogenesis gene signature with ccRCC histologic grade highlight opportunities for adjuvant combination VEGFR2 tyrosine kinase inhibitor and immune-checkpoint inhibition.
We conclude that TNF, acting through TNFR2, is an autocrine growth factor for ccRCC acting via Etk-VEGFR2 cross-talk, insights that may provide a more effective therapeutic approach to this disease.
Axitinib is an approved drug that targets the vascular endothelial growth factor receptor 2 (VEGFR2) and is licensed for second-line therapy of renal cell carcinoma.
Beyond well-validated signaling targets such as VHL, VEGFR and mTOR, additional pathways including HGF/c-MET and Wnt/β-catenin have emerged as important to RCC pathogenesis.
It has recently been approved by the European Medicines Agency (EMA) for first-line treatment of adult patients with advanced renal cell carcinoma (RCC) and for adult patients who are VEGFR and mammalian target of rapamycin (mTOR) pathway inhibitor-naive, following disease progression after one prior treatment with cytokine therapy for advanced RCC.
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.
The expression of VEGF and its receptors VEGFR-1 and VEGFR-2 in renal cell carcinoma (RCC) was investigated in the perspective of anti-VEGF treatments.
Structure-Based Virtual Screening for the Identification of High Affinity Compounds as Potent VEGFR2 Inhibitors for the Treatment of Renal Cell Carcinoma.
This study describes the relationship among proliferation, survival, and apoptosis with the expression of key molecules related to tumoral hypoxia (hypoxia-inducible factor (HIF)-1α, erythropoietin (EPO), vascular endothelial growth factor (VEGF)), their receptors (EPO-R, VEGFR-2), and stearoyl desaturase-1 (SCD-1) in early stages of ccRCC.
The aim of this study was to analyze the potential relationship between miRNA-185, VEGFR-2, and angiogenesis in samples from renal cell carcinoma (RCC) patients.
In this study, VEGFR-2 antibody (DC101) inhibited growth of RenCa renal cell carcinoma lung metastases by 26%, whereas VEGFR-1 antibody (MF-1) had no effect.
Tivozanib received its first global approval in EU, Iceland, and Norway on 28 August 2017 for the first-line treatment of adult patients with advanced RCC and for adult patients who are VEGFR and mTOR inhibitor-naive following disease progression after one prior treatment with cytokines.
There are phase 3 clinical trials underway evaluating anti-PD-L1 antibodies as adjuvant (postoperative) monotherapies for resectable renal cell carcinoma (RCC) and triple-negative breast cancer (TNBC); in combination with antiangiogenic VEGF/VEGFR2 inhibitors (e.g., bevacizumab and sunitinib) for metastatic RCC; and in combination with chemotherapeutics as neoadjuvant (preoperative) therapies for resectable TNBC.
Our data have important implications for combination therapy design, supporting the conclusion that targeting VEGFR2 alone in RCC has the potential to have pleiotropic effects on tumor stroma.
Nivolumab has emerged as a promising new therapy in advanced malignancies, and the first agent to show survival advantage in patients failing prior VEGFR-targeted therapy in metastatic RCC.