title: Present strategies in the treatment of metastatic renal cell carcinoma: an update on molecular targeting agents.
abstract: The understanding of cellular processes underlying tumour biology has allowed the development of novel molecular-targeted drugs with optimistic results in renal cell carcinoma (RCC). Mutations in the von Hippel-Lindau gene are found in 75% of sporadic RCCs, which results in upregulation of several genes involved in angiogenesis, e.g. vascular endothelial growth factor and platelet-derived growth factor. Other activated pathways in RCC are the epidermal growth factor receptor and the mTOR pathway, which regulate survival and cell growth. In addition to temsirolimus (an mTOR inhibitor) two different strategies have been studied to inhibit these targets: monoclonal antibodies, e.g. bevacizumab, and small molecule tyrosine-kinase inhibitors such as sorafenib, sunitinib and AG 013736. Phase II studies with these drugs reported substantial clinical activity in advanced RCC. Survival benefit was reported with temsirolimus, sunitinib and sorafenib in randomized trials, which led to the accelerated approval of sorafenib and sunitinib for advanced RCC by regulatory authorities in the USA and Europe. Nevertheless, as new therapies develop, new challenges arise for the optimum use of these targeted drugs. We discuss the rationale and the clinical development of these novel molecular-targeted agents, with special emphasis on updated information presented at recent meetings because of the relevance of the data reported and the potential future impact in the management of patients with RCC.
authors.affiliation: Oncology Department, Hospital del Mar, Barcelona, Spain. jbellmunt@imas.imim.es
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bellmunt
authors.forename: Clara
authors.initials: C
authors.lastname: Montagut
authors.forename: Santiago
authors.initials: S
authors.lastname: Albiol
authors.forename: Joan
authors.initials: J
authors.lastname: Carles
authors.forename: Pablo
authors.initials: P
authors.lastname: Maroto
authors.forename: Anna
authors.initials: A
authors.lastname: Orsola
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000098:blood supply / Q000188:drug therapy*; D005544:Forecasting; D006801:Humans; D007680:Kidney Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors