[Farnesyl transferase inhibitors: one target may be found in another].

Inserm U.563, Centre de Physiopathologie Toulouse Purpan, Département Innovation Thérapeutique et Oncologie Moléculaire, Institut Claudius Regaud, 20-24, rue du pont Saint-Pierre, 31052 Toulouse, France.
Medecine sciences: M/S (Impact Factor: 0.67). 03/2003; 19(2):211-6. DOI: 10.1051/medsci/2003192211
Source: PubMed


The fact that proteins such as Ras require farnesylation to induce malignant transformation prompted many investigators to design farnesyl transferase inhibitors (FTI) as novel anticancer drugs. FTIs inhibit the growth of ras transformed cells in vitro and induce tumor regression in ras dependent tumor in vivo. Moreover, FTIs inhibit tumor progression in human tumor xenograft models. Currently, FTIs are undergoing phase I and II trials in various cancer types. They show impressive antitumour efficacy and they lack toxicity. Despite these promising results, the development of such molecules in hindered by the absence of appropriate clinical endpoints and of surrogate biological markers. Indeed, it seems likely that Ras is not the critical target of FTIs and that inhibition of the farnesylation of proteins such as RhoB, might also contribute to the observed antitumour properties. Identification of targets that underlie their biological effect is essential in order to predict and evaluate their efficacy.

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Available from: Gilles Favre, Jan 28, 2016
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    • "Reducing the prenylation of proteins to treat NF1 has been recognized as a potential therapeutic approach. For example, the farnesyl transferase inhibitor (FTI) BMS-186511 (Mazieres et al., 2003) reduces proliferation of MPNST cell line ST88-14 (Yan et al., 1995), and FTI L-739,749 reduces proliferation of Nf-deficient mouse Schwann cells (Kim et al., 1997). A phase I clinical trial using FTI tipifarnib to treat plexiform neurofibromas was tolerated well in children, yet no objective responses were achieved (Widemann et al., 2006). "
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