Abstract
A gain-of-function mutation of c-kit is the crucial step in tumorigenesis of gastrointestinal stromal tumors (GIST). Imatinib can block the activated receptor tyrosine kinase activity of c-kit. These findings made GIST an ideal candidate for evaluation of new targeted therapeutic approaches. Clinical studies demonstrated that, with imatinib, objective responses can be reached in more than 50% of patients with advanced GIST. Furthermore, even in those patients with stable disease, long-term tumor control could be achieved. Therefore imatinib at a dose of 400 mg/day is now the standard treatment of advanced GIST in which RO-resection cannot be reached. As imatinib resistance in GIST occurs at a median of 18 to 26 months, further targeted therapies have been explored. Sunitinib, another tyrosine kinase inhibitor, seems to be useful especially in patients with exon 9 mutations of c-kit, who usually have a worse response to imatinib. This might indicate that more exactly targeted therapies in GIST might improve clinical outcomes in the future.
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Siehl, J., Thiel, E. (2007). C-kit, GIST, and Imatinib. In: Dietel, M. (eds) Targeted Therapies in Cancer. Recent Results in Cancer Research, vol 176. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-46091-6_12
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DOI: https://doi.org/10.1007/978-3-540-46091-6_12
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