Farnesyl transferase inhibitors: current developments and future perspectives

Ras oncogenes play an important role in carcinogenesis and are frequently f ound in various human tumour types. Cellular activity of Ras oncoprotein, r egulated through the enzyme farnesyl transferase, is crucial in the process of ras-dependent carcinogenesis, and therefore, specific inhibition of thi s enzyme is an attractive goal in anticancer treatment. Specific inhibitors of farnesyl transferase have been developed in recent years, many of them showing in vitro and in vivo growth inhibitory or cytostatic activity. Rece ntly results of the first clinical studies with various farnesyl transferas e inhibitors have been presented. In the design of phase I and II studies, either single-agent or combination studies, new endpoints have to be define d in order to properly assess feasibility antitumour activity and clinical valuability, (C) 2000 Harcourt Publishers Ltd.