Activation of the PI3 ' K-AKT pathway masks the proapoptotic effects of farnesyltransferase inhibitors

Farnesyltransferase inhibitors (FTIs) usually cause growth inhibition, but in certain preclinical settings they have been shown to induce apoptosis, a clinically desirable response. In this study, we show that the proapoptoti c effects of FTIs in Ras-transformed cells are masked by activation of phos phatidylinositol 3'-kinase (PI3'K) or AKT, which are controlled by cytokine s and integrins, The results implied that FTIs disrupt a signal that is cru cial for survival of malignant cells, but not normal cells, if the PI3'K-AK T pathway is inactivated. Our findings have implications for clinical appli cations of FTIs where apoptotic responses mould be preferred.