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Updated: Apr 26, 2026
Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
Targeting of histone deacetylases in brain tumors
Jonas Ecker1, Olaf Witt, Till Milde
1Clinical Cooperation Unit Pediatric Oncology (G340), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Abstract:
Histone deacetylase inhibitors (HDACis) have fascinated researchers in almost all fields of oncology for many years owing to their pleiotropic effects on nearly every aspect of cancer biology. Since the approval of the first HDACi vorinostat for the treatment of cutaneous T-cell leukemia in 2006, more than a hundred clinical trials have been initiated with a HDACi as a single agent or in combination therapy. Although a number of epigenetic and nonepigenetic molecular mechanisms of action have been proposed, biomarkers for response prediction and patient selection are still lacking. One of the inherent problems in the field of HDACis is their 'reverse' history of drug development: these compounds reached clinical application at an early stage, before the biology of their targets, HDAC1-11, was sufficiently understood. This review summarizes the current knowledge on the human family of HDACs as drug targets in pediatric and adult brain tumors, the efficacy and molecular action of HDACis in preclinical models, as well as the current status of the clinical development of these compounds in the field of neuro-oncology.
Insights
Histone deacetylase inhibitors show promise in brain tumor treatment, but lack biomarkers for patient selection. Further research is needed to understand their mechanisms and optimize their use in neuro-oncology.
Area of Science:
- Oncology
- Neuro-oncology
- Epigenetics
Background:
- Histone deacetylase inhibitors (HDACis) have demonstrated broad effects in cancer biology.
- Despite numerous clinical trials since 2006, biomarkers for predicting patient response to HDACis are still needed.
- The development of HDACis outpaced the understanding of their targets (HDAC1-11).
Purpose of the Study:
- To review the role of HDACs as drug targets in brain tumors.
- To summarize the efficacy and molecular mechanisms of HDACis in preclinical models.
- To outline the clinical development status of HDACis in neuro-oncology.
Main Methods:
- Literature review of HDAC inhibitors in neuro-oncology.
- Analysis of preclinical data on HDACi efficacy and mechanisms.
- Summary of ongoing clinical trials for HDAC inhibitors in brain tumors.
Main Results:
- HDACs are relevant drug targets in both pediatric and adult brain tumors.
- HDACis exhibit diverse molecular actions, affecting multiple cancer pathways.
- Clinical development of HDACis in neuro-oncology is ongoing but requires further optimization.
Conclusions:
- Understanding HDAC biology is crucial for effective HDAC inhibitor therapy in brain tumors.
- Development of predictive biomarkers is essential for patient selection and treatment success.
- Continued research into HDACis holds potential for improving brain tumor treatment outcomes.
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