Inhibition of farnesyltransferase induces regression of mammary and salivary carcinomas in ras transgenic mice - PubMed (original) (raw)
Inhibition of farnesyltransferase induces regression of mammary and salivary carcinomas in ras transgenic mice
N E Kohl et al. Nat Med. 1995 Aug.
Abstract
For Ras oncoproteins to transform mammalian cells, they must be post-translationally modified with a farnesyl group in a reaction catalysed by the enzyme farnesyl-protein transferase (FPTase). Inhibitors of FPTase have therefore been proposed as anti-cancer agents. We show that L-744,832, which mimics the CaaX motif to which the farnesyl group is added, is a potent and selective inhibitor of FPTase. In MMTV-v-Ha-ras mice bearing palpable tumours, daily administration of L-744,832 caused tumour regression. Following cessation of treatment, tumours reappeared, the majority of which regressed upon retreatment. No systemic toxicity was found upon necropsy of L-744,832-treated mice. This first demonstration of anti-FPTase-mediated tumour regression suggests that FPTase inhibitors may be safe and effective anti-tumour agents in some cancers.
Comment in
- Rational cancer therapy.
Lowy DR, Willumsen BM. Lowy DR, et al. Nat Med. 1995 Aug;1(8):747-8. doi: 10.1038/nm0895-747. Nat Med. 1995. PMID: 7585173 No abstract available.
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