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Inhibitors of prenyl transferases
1H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612-9497, USA.
Abstract:
Because farnesylation of Ras is required for its cancer-causing activity, several classes of farnesyl transferase inhibitors have recently been developed as potential anticancer drugs. During the last 12 months, important advances have been made in this field. In this review, we focus on three topics: targets of farnesyl transferase inhibitors other than Ras, alternative prenylation of K-Ras by the closely related prenyl transferase, geranyl geranyl transferase I, and the effects of geranyl geranyl transferase I inhibitors on cell cycle, apoptosis, and human tumor growth.
Insights
Farnesyl transferase inhibitors show promise as anticancer drugs. Recent research explores alternative prenylation pathways and the impact of geranyl geranyl transferase I inhibitors on cancer cell growth and death.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Farnesylation of Ras proteins is crucial for their oncogenic activity.
- Farnesyl transferase inhibitors (FTIs) are developed as potential anticancer agents.
- Recent advancements have been made in the field of FTIs.
Purpose of the Study:
- To review recent advances in farnesyl transferase inhibitor research.
- To explore targets of FTIs beyond Ras.
- To examine alternative prenylation of K-Ras by geranyl geranyl transferase I (GGT-I) and the effects of GGT-I inhibitors.
Main Methods:
- Literature review of recent studies on farnesyl transferase inhibitors.
- Analysis of research on GGT-I as an alternative prenylation enzyme.
- Evaluation of studies investigating GGT-I inhibitors' effects on cancer cells.
Main Results:
- FTIs have targets other than Ras.
- K-Ras can undergo alternative prenylation mediated by GGT-I.
- GGT-I inhibitors impact cell cycle, apoptosis, and human tumor growth.
Conclusions:
- Understanding alternative prenylation pathways is critical for developing effective anticancer therapies.
- GGT-I inhibitors represent a potential therapeutic strategy for cancers driven by K-Ras.
- Further research into GGT-I inhibition is warranted for cancer treatment.