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Published on: October 2, 2014
HDACs as an emerging target in endocrine tumors: a comprehensive review
Eckhard Klieser1,2, Bettina Neumayer1,2, Pietro Di Fazio3
1Institute of Pathology, Paracelsus Medical University/University Hospital Salzburg (SALK), Salzburg, Austria.
Introduction:
The pathogenic role of deregulated histone (de-)acetylation by histone deacetyles (HDACs) has been demonstrated in several human cancers. While some HDAC inhibitors (HDACi) have been approved for individual entities, for endocrine tumors such translation into clinical practice has not yet been achieved.
Areas Covered:
Relevant results identified by structured searches in PubMed as well as in reference lists are summarized in a narrative review to discuss the current knowledge of HDAC involvement and their therapeutic relevance in endocrine tumors. For thyroid, neuroendocrine, and adrenal tumors, various oncogenic mechanisms of HDAC deregulation and effects of HDAC inhibitors (HDACi) have been identified in preclinical studies including direct cancer cell toxicity and modification of differentiation status.
Expert Opinion:
Based on positive pre-clinical results, the research on HDAC (inhibition) in the various endocrine tumors should be intensified - yet, it needs to be considered that i) HDACs' oncogenic actions might constitute only a part of epigenetic mechanisms driving cancer, ii) individual HDAC has different roles in different endocrine tumor entities, iii) inhibition of HDACs might be especially attractive in combination with conventional or other targeted therapies, and iv) new HDAC-inhibiting drugs with improved specificity or functionally modified HDACi might further improve their efficacy.
Insights
Histone deacetylase inhibitors (HDACi) show promise for endocrine tumors, but clinical application is limited. Further research is needed to explore HDAC inhibition
Area of Science:
- Epigenetics and Cancer Biology
- Molecular Oncology
- Endocrinology
Background:
- Deregulation of histone acetylation by histone deacetylases (HDACs) is implicated in various human cancers.
- While some histone deacetylase inhibitors (HDACi) are approved for certain cancers, their clinical use in endocrine tumors is not yet established.
- Preclinical studies reveal HDAC deregulation and the effects of HDAC inhibitors (HDACi) in thyroid, neuroendocrine, and adrenal tumors.
Approach:
- A narrative review summarizing current knowledge on HDAC involvement in endocrine tumors.
- Analysis of preclinical data on HDAC deregulation and HDAC inhibitor efficacy.
- Identification of oncogenic mechanisms and therapeutic relevance.
Key Points:
- HDAC deregulation plays a pathogenic role in endocrine tumors.
- HDAC inhibitors demonstrate anti-cancer effects, including direct toxicity and differentiation modulation, in preclinical models.
- Despite positive preclinical findings, clinical translation of HDAC inhibitors for endocrine tumors is pending.
Conclusions:
- Intensified research into HDAC inhibition for endocrine tumors is warranted, considering the complexity of epigenetic mechanisms.
- Individual HDACs may have distinct roles across different endocrine tumor types.
- Combination therapies involving HDAC inhibitors may enhance efficacy, alongside the development of more specific HDAC inhibitors.
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