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Updated: Jun 18, 2026
Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
Targeting histone deacetylases in pancreatic ductal adenocarcinoma
Günter Schneider1, Oliver H Krämer, Petra Fritsche
1Technische Universität München, Klinikum rechts der Isar, II. Medizinische Klinik, München, Germany. guenter.schneider@lrz.tum.de
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) is a dismal disease with a median survival below 6 months and a 5-year survival rate below 1%. Effective therapies for locally advanced or metastatic tumours are missing and curatively resected patients relapse in over 80% of the cases. Although histone deacetylases (HDACs) are involved in the control of proliferation, apoptosis, differentiation, migration and angiogenesis of cancer cells, knowledge about the expression patterns and functions of individual HDAC isoenzymes in pancreatic cancer is sparse. This review summarizes the roles of HDACs as novel therapeutic targets and the molecular mode of action of HDAC-inhibitors (HDACI) in PDACs. Success of HDACI in clinical settings will depend on an increased knowledge of HDAC functions as well as on a better understanding of the mode of action of HDACI. Pre-clinical experimental data that constitute the basis for rational therapeutic strategies to treat PDAC are described here. Translating these rational-based therapies into the clinic will finally increase our chance to establish an effective HDACI-containing combination therapy effective against PDAC.
Insights
Pancreatic ductal adenocarcinoma (PDAC) remains a deadly cancer with limited treatment options. This review explores histone deacetylase inhibitors (HDACIs) as a promising therapeutic strategy for PDAC, highlighting pre-clinical data for future clinical trials.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis with high mortality rates.
- Current therapies for advanced or metastatic PDAC are insufficient, and recurrence is common even after curative surgery.
- The role of specific histone deacetylase (HDAC) isoenzymes in PDAC development and progression is not well understood.
Purpose of the Study:
- To review the current understanding of HDACs as therapeutic targets in PDAC.
- To summarize the molecular mechanisms of HDAC inhibitors (HDACIs) in PDAC.
- To discuss pre-clinical data supporting rational therapeutic strategies involving HDACIs for PDAC treatment.
Main Methods:
- Literature review of pre-clinical studies on HDACs and HDACIs in PDAC.
- Analysis of the expression patterns and functions of individual HDAC isoenzymes in pancreatic cancer.
- Synthesis of data on the molecular mode of action of HDACIs.
Main Results:
- HDACs play crucial roles in cancer cell proliferation, apoptosis, differentiation, migration, and angiogenesis.
- Knowledge regarding the specific functions of individual HDAC isoenzymes in PDAC is limited.
- Pre-clinical data suggest that HDACIs hold potential as therapeutic agents for PDAC.
Conclusions:
- HDACs represent promising novel therapeutic targets for PDAC.
- Further understanding of HDAC functions and HDACI mechanisms is essential for clinical success.
- Translating pre-clinical findings into effective HDACI-based combination therapies could improve outcomes for PDAC patients.
