부산대학교 도서관

This paper reviews the recent progress in understanding the molecular basis of RCC tumourigenesis, and the development and application of new therapies targeted at key molecules involved in angiogenesis, a key process in tumour growth and progression, in order to address the treatment approaches with multitargeted therapies in advanced RCC. We reviewed the international recent literature using Pubmed search. RCC is genetically linked to factors regulating angiogenesis, in particular vascular endothelial growth factor (VEGF). Sunitinib is a multitarget receptor tyrosine-kinase (TK) inhibitor, acting on VEGF receptor (VEGFR) and platelet-derived growth factor receptors (PDGFR). Sorafenib is an oral multikinase inhibitor (VEGFR and PDGFR) showing also inhibitors effect on the Raf system. Similar compound, axitinib, is now in clinical development and directly inhibit the VEGF and PDGF receptors (VEGFR and PDGFR). Bevacizumab is a recombinant human antibody against VEGF binds and it neutralizes all biologically active isoforms of VEGF. Phase I trials showed a consistent safety profile with these new therapies. Phase II and phase III trials showed that these antiangiogenic agents are effective in the treatment of advanced RCC. Survival benefits exist in particular when advanced RCC patients undergo cytoreductive nephrectomies before the initiation of the systemic therapy. Although patients with mRCC are now offered a better prognosis, several questions remain: how to optimise the clinical use of new agents; differences among different compounds; the identification of patients most likely to benefit from multitargeted therapy; advantages of combination or sequential therapies. The new targeted therapies have showed therapeutic feasibility and efficacy, leading to dramatically improvement in survival, both progression-free and overall, and with acceptable toxicity. Multitargeted therapy with Sunitinib and Sorafenib has been approved to FDA and is revolutioning how we clinically approach advanced RCC. [ABSTRACT FROM AUTHOR]