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BioMed Research International
Volume 2013 (2013), Article ID 419176, 9 pages
http://dx.doi.org/10.1155/2013/419176
Review Article

Progress of Molecular Targeted Therapies for Advanced Renal Cell Carcinoma

1Department of Clinical and Specialist Sciences, Urology, Polytechnic University of the Marche Region, AOU Ospedali Riuniti Umberto I-GM Lancisi and G Salesi, Ancona, Italy
2Medical Oncology, Polytechnic University of the Marche Region, AOU Ospedali Riuniti Umberto I-GM Lancisi and G Salesi, Ancona, Italy
3School of Pharmacy, Section of Experimental Medicine, University of Camerino, Italy

Received 30 April 2013; Revised 13 July 2013; Accepted 3 August 2013

Academic Editor: Jeanny B. Aragon-Ching

Copyright © 2013 Alessandro Conti et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Vascular endothelial growth factor (VEGF) plays a crucial role in tumor angiogenesis. VEGF expression in metastatic renal cell carcinoma (mRCC) is mostly regulated by hypoxia, predominantly via the hypoxia-induced factor (HIF)/Von Hippel-Lindau (VHL) pathway. Advances in our knowledge of VEGF role in tumor angiogenesis, growth, and progression have permitted development of new approaches for the treatment of mRCC, including several agents targeting VEGF and VEGF receptors: tyrosine kinase pathway, serine/threonine kinases, α5β1-integrin, deacetylase, CD70, mammalian target of rapamycin (mTOR), AKT, and phosphatidylinositol 3′-kinase (PI3K). Starting from sorafenib and sunitinib, several targeted therapies have been approved for mRCC treatment, with a long list of agents in course of evaluation, such as tivozanib, cediranib, and VEGF-Trap. Here we illustrate the main steps of tumor angiogenesis process, defining the pertinent therapeutic targets and the efficacy and toxicity profiles of these new promising agents.