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• W2128725149 abstract "Farnesylation of the oncoprotein Ras is required for its cancer-causing activity. We have designed farnesyltransferase inhibitor (FTI)-276, a tetrapeptide mimetic of the carboxyl terminus of K-Ras4B, as a highly potent and selective inhibitor of Ras farnesylation in vitro and in vivo. FTI-276 blocked the growth in nude mice of a human lung carcinoma that expresses the two most prevalent genetic alterations in human cancers (K-Ras oncogenic mutation and deletion in the tumor suppressor gene p53). In contrast, FTI-276 did not inhibit tumor growth of a human lung carcinoma that harbors no Ras mutations. Furthermore, FTI-276 inhibited oncogenic signaling and tumor growth of NIH 3T3 cells transformed with the ras but not the raf oncogene. Inhibition of tumor growth in vivo was dose dependent and correlated with inhibition of Ras processing in tumors in vivo. The work described here identifies FTI-276 as a highly selective suppressor of Ras-dependent oncogenicity and suggests that a broad spectrum of human cancers with aberrant Ras function could benefit from farnesyltransferase inhibitor treatment." @default.
• W2128725149 created "2016-06-24" @default.
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• W2128725149 date "1995-10-01" @default.
• W2128725149 modified "2023-10-12" @default.
• W2128725149 title "Ras CAAX peptidomimetic FTI 276 selectively blocks tumor growth in nude mice of a human lung carcinoma with K-Ras mutation and p53 deletion." @default.
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