Abstract
This review highlights therapeutic agents from recent cancer therapeutic trials showing the greatest potential for further clinical use for sunitinib in the near future. In fact, sunitinib is one of multi-tyrosine kinase inhibitors; tyrosine kinases are enzymes, which transfer phosphate groups from ATP to the hydroxyl group of tyrosine residues on signal transduction molecules. Phosphorylation of signal transduction molecules, in turn, induces dramatic changes in tumor growth, including activation of angiogenesis and DNA synthesis. Therefore, sustain efforts have been directed for developing inhibitors for angiogenesis, which is the marginal process for tumor growth and development through targeting TKs. Almost if not all angiogenesis inhibitors target the vascular endothelial growth factor (VEGF) signaling pathway.
Highlights
The accumulation of hypoxia inducible factor induces the expression of hypoxia-inducible genes, e.g. vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) [1,2,3]
Angiogenesis inhibitors, such as the monoclonal antibody bevacizumab (Avastin, Genentech/Roche) and two kinase inhibitors sunitinib (SU11248, Sutent, Pfizer) and sorafenib (BAY43-9006, Nexavar, Bayer) [4] target the vascular endothelial growth factor (VEGF) signaling pathway. Upon binding of these growth factors to their respective tyrosine kinase receptors, the cell migration, proliferation and survival take place [5]. It acts as a multi-targeted tyrosine kinase inhibitor, sunitinib has widely recommended in the clinic (Figure 1)
Of note the incidence of apoptosis in cancer cells as a result of exposed sunitinib is correlated with reduced activation of STAT3, which has adverse effects on chemotherapy sensitivity even in the case of solid tumors [13]
Summary
The accumulation of hypoxia inducible factor induces the expression of hypoxia-inducible genes, e.g. VEGF and platelet-derived growth factor (PDGF) [1,2,3] Angiogenesis inhibitors, such as the monoclonal antibody bevacizumab (Avastin, Genentech/Roche) and two kinase inhibitors sunitinib (SU11248, Sutent, Pfizer) and sorafenib (BAY43-9006, Nexavar, Bayer) [4] target the vascular endothelial growth factor (VEGF) signaling pathway. Upon binding of these growth factors to their respective tyrosine kinase receptors, the cell migration, proliferation and survival take place [5]. The small molecule receptor tyrosine kinase inhibitors (RTKs), including VEGFR, PDGFR and KIT, are expressed on many if not all tumors [8,9], sunitinib may have potential for use in several tumors types
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