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sunitinib

Tuesday 2 June 2009

Definition: Sunitinib (marketed as Sutent, and previously known as SU11248) is an oral, small-molecule, multi-targeted receptor tyrosine kinase (RTKs) inhibitor (multiRTKs inhibitors).

Sunitinib was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST) on January 26, 2006.

The concept was of a ATP analogue that would compete with ATP for binding to the catalytic site of receptor tyrosine kinases. This concept led to the invention of many small-molecule tyrosine kinase inhibitors including Gleevec (imatinib), Sutent (sunitinib), Tarceva (erlotinib) and many other cancer drugs.

Targets

Sunitinib inhibits cellular signaling by targeting multiple RTKs.

These include all platelet-derived growth factor receptors (PDGFRs) and vascular endothelial growth factor receptors (VEGFRs), which play a role in both tumor angiogenesis and tumor cell proliferation.

The simultaneous inhibition of these targets therefore leads to both reduced tumor vascularization and cancer cell death, and ultimately tumor shrinkage.

Sunitinib also inhibits KIT (CD117), one of the the RTKs that drives the majority of GISTs.

In addition, sunitinib inhibits other RTKs. These include:

- RET
- CSF1R
- FLT3 (flt3)

Indications

- clear cell renal cell carcinoma
- gastrointestinal stromal tumor (GIST)

The efficacy of sunitinib is currently being evaluated in a broad range of solid tumors, including breast, lung, and colorectal cancers. Early studies have shown single-agent efficacy in a number of different areas.

Links

- WKP

References

- VEGF expression is related to good response and long progression-free survival in gastrointestinal stromal tumor patients treated with Sunitinib. Koh Y, Lee HE, Im SA, Kim SH, Kim TM, Han SW, Oh DY, Kim JH, Lee SH, Kim DW, Kim TY, Kim WH, Heo DS, Bang YJ. Diagn Mol Pathol. 2011 Sep;20(3):143-7. PMID: #21817899#

- A Case of Adult Metastatic Xp11 Translocation Renal Cell Carcinoma Treated Successfully With Sunitinib. Choueiri TK, Mosquera JM, Hirsch MS. Clin Genitourin Cancer. 2009 Oct 1;7(3):E93-E94. PMID: #19815489#