Abstract
Drugs that target the vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) pathways have revolutionized the treatment of patients with metastatic renal cell cancer (RCC). Patients with clear cell RCC often have mutations or silencing of the von Hippel Lindau gene leading to an accumulation of HIF 1 alpha. This allows growth factors such as VEGF and PDGF to be upregulated to promote angiogenesis and endothelial stabilization. Both sunitinib and sorafenib target VEGF and PDGF receptor tyrosine kinases while bevacizumab is a monoclonal antibody to VEGF. These three agents have demonstrated superior progression free survival in patients with metastatic RCC when compared to interferon or placebo. Newer anti-VEGF agents such as axitinib, pazopanib and cediranib are currently under investigation to elucidate future treatment options. The mammalian target of rapamycin (mTOR) is downstream of the VEGF pathway and has been targeted with drugs including temsirolimus and everolimus. This review will detail the pharmacologic and molecular activity of these agents and how they translate into clinical efficacy.
Keywords: Vascular endothelial growth factor, platelet derived growth factor, renal cell carcinoma, sunitinib, sorafenib
Current Cancer Drug Targets
Title: Anti-Angiogenic Targets in the Treatment of Advanced Renal Cell Carcinoma
Volume: 8 Issue: 8
Author(s): Daniel Y.C. Heng and Ronald M. Bukowski
Affiliation:
Keywords: Vascular endothelial growth factor, platelet derived growth factor, renal cell carcinoma, sunitinib, sorafenib
Abstract: Drugs that target the vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) pathways have revolutionized the treatment of patients with metastatic renal cell cancer (RCC). Patients with clear cell RCC often have mutations or silencing of the von Hippel Lindau gene leading to an accumulation of HIF 1 alpha. This allows growth factors such as VEGF and PDGF to be upregulated to promote angiogenesis and endothelial stabilization. Both sunitinib and sorafenib target VEGF and PDGF receptor tyrosine kinases while bevacizumab is a monoclonal antibody to VEGF. These three agents have demonstrated superior progression free survival in patients with metastatic RCC when compared to interferon or placebo. Newer anti-VEGF agents such as axitinib, pazopanib and cediranib are currently under investigation to elucidate future treatment options. The mammalian target of rapamycin (mTOR) is downstream of the VEGF pathway and has been targeted with drugs including temsirolimus and everolimus. This review will detail the pharmacologic and molecular activity of these agents and how they translate into clinical efficacy.
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Cite this article as:
Heng Y.C. Daniel and Bukowski M. Ronald, Anti-Angiogenic Targets in the Treatment of Advanced Renal Cell Carcinoma, Current Cancer Drug Targets 2008; 8 (8) . https://dx.doi.org/10.2174/156800908786733450
DOI https://dx.doi.org/10.2174/156800908786733450 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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