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Updated: May 28, 2026

A Fluorescence-based Protocol for Preliminary Screening of Protein Synthesis Inhibitors from Natural Sources
Published on: January 27, 2026
Targeting protein prenylation for cancer therapy
Norbert Berndt1, Andrew D Hamilton, Saïd M Sebti
1Drug Discovery Department, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, Florida 33612, USA.
Abstract:
Protein farnesylation and geranylgeranylation, together referred to as prenylation, are lipid post-translational modifications that are required for the transforming activity of many oncogenic proteins, including some RAS family members. This observation prompted the development of inhibitors of farnesyltransferase (FT) and geranylgeranyl-transferase 1 (GGT1) as potential anticancer drugs. In this Review, we discuss the mechanisms by which FT and GGT1 inhibitors (FTIs and GGTIs, respectively) affect signal transduction pathways, cell cycle progression, proliferation and cell survival. In contrast to their preclinical efficacy, only a small subset of patients responds to FTIs. Identifying tumours that depend on farnesylation for survival remains a challenge, and strategies to overcome this are discussed. One GGTI has recently entered the clinic, and the safety and efficacy of GGTIs await results from clinical trials.
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