Elucidating Mechanisms of Farnesyltransferase Inhibitor Action and Resistance in Breast Cancer by Bioluminescence Imaging

: Prenyltransferase inhibitors (FTIs & GGTIs) block post-translational processing of Ras-like GTPases that have key roles in breast cancer. However, FTIs have yet to be used widely in breast cancer therapy because it is not yet possible to identify patients likely to be FTI-sensitive or to use combinatorial therapy to broaden the spectrum of patients that respond to FTIs. A new lentiviral-based prenylation responsive bioluminescence reporter system has been constructed and validated in human breast cancer cell lines. Our strategy should offer the opportunity to visualize over time the action of FTIs and GGTIs toward specific, biologically relevant prenylation-dependent proteins in tumors of living animals in vivo.