Sunitinib gastrointestinal stromal tumor

George, S. (2007) Sunitinib, a multitargeted tyrosine kinase inhibitor, in the management of gastrointestinal stromal tumor. Curr Oncol Rep 9(4), 323-327. 

Gastrointestinal stromal tumor (GIST) Mutation c-KIT c-KIT(tyrosi ne-kinase activity) Imatinib, Dasatinib, Sunitinib... 

In summary, sunitinib maleate (1) is a multitargeted receptor tyrosine kinase inhibitor with potent anti-angiogenic and antitumor activity. It is approved for the treatment of advanced renal cell carcinoma and gastrointestinal stromal tumors, and is currently undergoing clinical trials for a number of additional malignancies. The discovery synthesis of 1 along with its process development approaches were described in this chapter. 

Goodman VL, Rock EP, Dagher R, et al. Approval summary Sunitinib for the treatment of imatinib refractory or intolerant gastrointestinal stromal tumors and advanced renal cell carcinoma. Clin Cancer Res. 2007 13(5) 1367-1373. 

Inhibitor resistance mutants have also been identified in tumors from patients with gastrointestinal stromal tumors (GISTs).38 These tumors are driven by activating mutations of KIT and PDGFRa receptor tyrosine kinases.39 Both imatinib and sunitinib are indicated to treat surgically inoperable GISTs. However, complete responses are rare and many patients go on to develop secondary resistance.40... 

Sunitinib (7),10 developed by Sugene/Pfizer, was approved in 2006 for the treatment of renal cell carcinoma (RCC). It is a VEGFR kinase inhibitor that slows down the angiogenesis of tumor endothelial cells, which provide nutrients and help tumor growth and metastasis. Sunitinib also blocks KIT, an oncogenic kinase that causes gastrointestinal stromal cell tumors. It was approved as a second-line anti-GSIT therapy for imatinib-resistant patients. 

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