title: Antiangiogenic treatments and mechanisms of action in renal cell carcinoma.
abstract: Several angiogenic mechanisms are involved in the pathology of renal cell carcinoma (RCC). Increasing knowledge of angiogenesis and the associated signalling pathways has led to the development of targeted antiangiogenic agents for the treatment of metastatic RCC and the introduction of these agents has significantly improved outcomes for these patients. This article provides an overview of the angiogenic mechanisms implicated in RCC, focusing on the main vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and mammalian target of rapamycin (mTOR) signalling pathways. Targeted antiangiogenic agents for the treatment of mRCC include receptor tyrosine kinase inhibitors (such as sunitinib, sorafenib, pazopanib, axitinib, cediranib and tivozanib), monoclonal antibodies (such as bevacizumab) and mTOR inhibitors (such as temsirolimus and everolimus). In this article, we consider the modes of action of these targeted agents and their differing target receptor profiles and we also evaluate how these correlate with their clinical efficacy and tolerability profiles.
authors.affiliation: Université de Lyon-Centre Léon Berard, 28 rue Laennec, 69373 Lyon cedex 08, France. negrier@lyon.fnclcc.fr
authors.forename: Sylvie
authors.initials: S
authors.lastname: Négrier
authors.forename: Eric
authors.initials: E
authors.lastname: Raymond
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008954:Models, Biological; D009362:Neoplasm Metastasis; D010818:Practice Patterns, Physicians'
chemical_list: D020533:Angiogenesis Inhibitors