Article

A preclinical review of sunitinib, a multitargeted receptor tyrosine kinase inhibitor with anti-angiogenic and antitumour activities

Pfizer Global Research and Development, 10724 Science Center Drive, San Diego, CA 92121, USA.
Annals of Oncology (Impact Factor: 6.58). 10/2007; 18 Suppl 10(suppl 10):x3-10. DOI: 10.1093/annonc/mdm408
Source: PubMed

ABSTRACT Sunitinib malate is an oral, multitargeted tyrosine kinase inhibitor that targets both angiogenic pathways (i.e., vascular endothelial growth factor receptor and platelet-derived growth factor receptor) and direct pro-oncogenic pathways (e.g., stem-cell factor receptor and FMS-like tyrosine kinase-3). Preclinical studies with this agent have indicated that it exhibits robust inhibitory activity against these targets. Clinical trial results have demonstrated the therapeutic potential of this agent and have implicated sunitinib targets in the pathophysiology of malignancies such as renal cell carcinoma and gastrointestinal stromal tumour. This paper reviews the preclinical data supporting the development of this agent and its translation from benchtop to bedside. It also highlights the importance of the multiple pathways that may be involved in cancer progression and the importance of these pathways in selected malignancies.

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    • "Meanwhile, the indirect inhibitors of angiogenesis interfere in the pro-angiogenic communication between the tumor cells and the endothelial cells (Folkman et al., 1998). SU5416 is a tyrosine kinase lipophilic synthetic inhibitor (TKI), indirect inhibitor of angiogenesis that blocks the phosphorylation of VEGF receptor, and has potent antiangiogenic properties in preclinical studies (Fong et al., 1999; Abdollahi et al., 2003; Christensen, 2007). On the other hand, the TNP-470 direct angiogenesis inhibitor, a fumagillin analog , has a potent cytostatic action in endothelial cells and also significant antitumor properties (Masiero et al., 1997; Folkman, 2005). "
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    • "Finally, increased visible lung surface nodules and lung weight were indicative of increased tumor burden in both tumor models, with representative hematoxylin and eosin (H&E) and anti-vimentin staining shown in Figure 3D. Since previously published studies had demonstrated potent tumor growth inhibition of established primary tumors in mice after sunitinib treatment (Christensen, 2007), we compared short-term and sustained sunitinib therapies in both orthotopic primary tumor and experimental metastasis models. 231/LM2-4 LUC+ cells were implanted into the mammary fat pad of nu/nu mice and treated "
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