John Libbey Eurotext

Hématologie

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Preclinical and clinical development of farnesyl transferase inhibitors: perspectives in hematology Volume 11, issue 4, Juillet-Août 2005

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Authors
INSERM U563, CPTP, Département innovation thérapeutique et oncologie moléculaire, institut Claudius-Regaud, université Paul-Sabatier, 20-24 rue du Pont Saint–Pierre, 31052 Toulouse Cedex 3, Centre hospitalier universitaire Purpan, service d’hématologie, Toulouse
  • Key words: farnesyl transferase inhibitors, hematologic malignancies, Ras GTPasis
  • Page(s) : 277-85
  • Published in: 2005

The discovery that the transforming activity of oncogenic Ras depends upon its post-translational farnesylation has led to the development of farnesyl transferase inhibitors (FTIs). Preclinical data shows the potency of FTIs to inhibit the growth of ras-transformed cells in vitro and to induce tumor regression in Ras-dependent tumors. Currently, FTIs are undergoing clinical trials in various solid tumor with variable results. Based on the our better knowledge of leucemogenesis and in particular the activation of Ras signaling pathways, FTIs have been tested in hematologic malignacies with promising results. In this review, we report the results of the main recent clinical trials and we focus on the cellular effects (antiproliferative, pro-apoptotic and anti-angiogenic) of FTIs, with an emphasis on potential FTIs targets. Unraveling the biological basis by which FTIs exert their effect remains a priority in order to precise their optimal use.