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Focus on deacetylation for therapeutic benefit
Shabana Shabbeer1, Michael A Carducci
1Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
Idrugs : the Investigational Drugs Journal
|February 8, 2005
Summary
Histone deacetylase inhibitors (HDACIs) can re-express silenced genes in cancer cells. These epigenetic modifiers also show anti-cancer effects alone or in combination therapies, driving clinical investigation.
Area of Science:
- Epigenetics
- Cancer Biology
- Pharmacology
Background:
- Cancer cells often silence crucial genes.
- Epigenetic modifiers, like histone deacetylase inhibitors (HDACIs), can re-express these silenced genes.
- HDACIs exhibit multiple anti-cancer mechanisms beyond gene re-expression.
Purpose of the Study:
- To review the cellular and biological effects of HDACIs.
- To explore the efficacy of HDACIs alone and in combination therapies.
- To summarize ongoing and completed clinical trials involving HDACIs.
Main Methods:
- Review of preclinical and clinical studies on HDACIs.
- Analysis of structure-activity relationships of HDACIs.
- Compilation of data from cancer clinical trials.
Main Results:
- HDACIs re-express silenced genes and have pleiotropic anti-cancer effects.
- Combination therapies with HDACIs enhance anti-proliferative activity.
- Improved HDACIs have been designed based on structure-activity relationships.
Conclusions:
- HDACIs are promising epigenetic drugs for cancer therapy.
- Their broad biological effects and low toxicity support clinical investigation.
- Further research and clinical trials are ongoing to optimize HDACI-based treatments.