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Role of histone deacetylases in pancreas: Implications for pathogenesis and therapy
Eckhard Klieser1, Stefan Swierczynski1, Christian Mayr1
1Eckhard Klieser, Johanna Schmidt, Daniel Neureiter, Romana Illig, Institute of Pathology, Paracelsus Medical University, Salzburger Landeskliniken (SALK), 5020 Salzburg, Austria.
Abstract:
In the last years, our knowledge of the pathogenesis in acute and chronic pancreatitis (AP/CP) as well as in pancreatic cancerogenesis has significantly diversified. Nevertheless, the medicinal therapeutic options are still limited and therapeutic success and patient outcome are poor. Epigenetic deregulation of gene expression is known to contribute to development and progression of AP and CP as well as of pancreatic cancer. Therefore, the selective inhibition of aberrantly active epigenetic regulators can be an effective option for future therapies. Histone deacetylases (HDACs) are enzymes that remove an acetyl group from histone tails, thereby causing chromatin compaction and repression of transcription. In this review we present an overview of the currently available literature addressing the role of HDACs in the pancreas and in pancreatic diseases. In pancreatic cancerogenesis, HDACs play a role in the important process of epithelial-mesenchymal-transition, ubiquitin-proteasome pathway and, hypoxia-inducible-factor-1-angiogenesis. Finally, we focus on HDACs as potential therapeutic targets by summarizing currently available histone deacetylase inhibitors.
Insights
Aberrantly active epigenetic regulators, like histone deacetylases (HDACs), drive pancreatic diseases. Inhibiting these HDACs offers a promising therapeutic strategy for pancreatitis and pancreatic cancer.
Area of Science:
- Molecular Biology
- Oncology
- Gastroenterology
Background:
- Pancreatitis and pancreatic cancer pathogenesis are complex.
- Current therapeutic options for these conditions are limited, with poor patient outcomes.
- Epigenetic deregulation significantly contributes to the development and progression of pancreatic diseases.
Purpose of the Study:
- To review the role of histone deacetylases (HDACs) in pancreatic diseases.
- To explore HDACs as potential therapeutic targets for pancreatitis and pancreatic cancer.
- To summarize available HDAC inhibitors for future therapies.
Main Methods:
- Literature review of HDACs in pancreatic pathogenesis.
- Analysis of HDAC involvement in key cancer processes like epithelial-mesenchymal transition.
- Summary of current histone deacetylase inhibitors.
Main Results:
- Histone deacetylases (HDACs) are implicated in pancreatic cancerogenesis.
- HDACs play roles in epithelial-mesenchymal transition, the ubiquitin-proteasome pathway, and angiogenesis.
- Aberrantly active HDACs represent viable therapeutic targets.
Conclusions:
- Targeting epigenetic regulators, specifically HDACs, presents a promising therapeutic avenue.
- Inhibition of HDACs may offer improved treatment strategies for acute and chronic pancreatitis and pancreatic cancer.
- Further research into HDAC inhibitors is warranted for pancreatic disease treatment.
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