Sunitinib malate, an orally available small molecule, inhibits multiple RTKs that are implicated in tumor growth, pathologic angiogenesis, and the metastatic progression of cancer.1
- Two important RTKs implicated in tumor angiogenesis, vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR), are expressed in many types of solid tumors2
- VEGFR-1, -2, and -3 are found on the surfaces of endothelial cells that form the walls of blood vessels, and each plays a distinct role in essential processes, including3,4:
- Tumor angiogenesis
- Lymphangiogenesis
- Metastasis
- PDGFRs are expressed on pericytes, which provide structural support to the endothelial cells. PDGFR-ß is thought to regulate the proliferation and migration of pericytes to new vessels during angiogenesis, and is required for the maturation and maintenance of tumor blood vessels5-7
- Sunitinib demonstrates anti-angiogenic activity by inhibiting VEGFR-1, -2, and -3 on endothelial cells and PDGFR-α and -ß. Sunitinib also inhibits other targets important to tumor growth, such as KIT, FLT3, and RET1,5
- Breast
- Non-small cell lung
- Colorectal
- Prostate
- Hepatocellular
- Renal cell carcinoma (RCC)
- Gastrointestinal stromal tumor (GIST)
- Gastric
Sunitinib malate is not indicated for the treatment of breast, non-small cell lung, colorectal, prostate, hepatocellular, or gastric cancer. Sunitinib malate is indicated for patients with advanced renal cell carcinoma (RCC) and gastrointestinal stromal tumor (GIST) after disease progression on or intolerance to imatinib mesylate.
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Information in the Oncology Investigational Pipeline relates to therapies currently being researched.
References: 1. Data on file. Pfizer Inc, New York, NY. 2. Bergers G, Song S, Meyer-Morse N, Bergsland E, Hanahan D. Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J Clin Invest. 2003;111:1287-1295. 3. Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 2005;23:1011-1027. 4. Ferrara N, Gerber H-P, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9:669-676. 5. Mendel DB, Laird AD, Xin X, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res. 2003;9:327-337. 6. Erber R, Thurnher A, Katsen AD, et al. Combined inhibition of VEGF- and PDGF-signaling enforces tumor vessel regression by interfering with pericyte-mediated endothelial cell survival mechanisms. FASEB J. 2004;8:338-340. 7. Thommen R, Humar R, Misevic G, et al. PDGF-BB increases endothelial migration and cord movements during angiogenesis in vitro. J Cell Biochem. 1997;64:403-413.
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