Related Experiment Video
Updated: Nov 18, 2025
Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS
Published on: August 10, 2017
Anticancer Therapy with HDAC Inhibitors: Mechanism-Based Combination Strategies and Future Perspectives
Robert Jenke1,2, Nina Reßing3, Finn K Hansen3
1University Cancer Center Leipzig (UCCL), University Hospital Leipzig, D-04103 Leipzig, Germany.
Abstract:
The increasing knowledge of molecular drivers of tumorigenesis has fueled targeted cancer therapies based on specific inhibitors. Beyond "classic" oncogene inhibitors, epigenetic therapy is an emerging field. Epigenetic alterations can occur at any time during cancer progression, altering the structure of the chromatin, the accessibility for transcription factors and thus the transcription of genes. They rely on post-translational histone modifications, particularly the acetylation of histone lysine residues, and are determined by the inverse action of histone acetyltransferases (HATs) and histone deacetylases (HDACs). Importantly, HDACs are often aberrantly overexpressed, predominantly leading to the transcriptional repression of tumor suppressor genes. Thus, histone deacetylase inhibitors (HDACis) are powerful drugs, with some already approved for certain hematological cancers. Albeit HDACis show activity in solid tumors as well, further refinement and the development of novel drugs are needed. This review describes the capability of HDACis to influence various pathways and, based on this knowledge, gives a comprehensive overview of various preclinical and clinical studies on solid tumors. A particular focus is placed on strategies for achieving higher efficacy by combination therapies, including phosphoinositide 3-kinase (PI3K)-EGFR inhibitors and hormone- or immunotherapy. This also includes new bifunctional inhibitors as well as novel approaches for HDAC degradation via PROteolysis-TArgeting Chimeras (PROTACs).
Insights
Histone deacetylase inhibitors (HDACis) show promise in cancer therapy by reversing aberrant gene silencing. This review explores their efficacy in solid tumors and novel combination strategies for enhanced treatment outcomes.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Targeted cancer therapies leverage molecular drivers of tumorigenesis.
- Epigenetic modifications, particularly histone acetylation regulated by HATs and HDACs, are crucial in cancer progression.
- Aberrant HDACs often repress tumor suppressor genes, making HDAC inhibitors (HDACis) a key therapeutic strategy.
Purpose of the Study:
- To review the capability of HDACis in influencing cancer pathways.
- To provide a comprehensive overview of preclinical and clinical studies on HDACis in solid tumors.
- To highlight strategies for enhancing HDACi efficacy through combination therapies and novel drug development.
Main Methods:
- Review of preclinical and clinical studies on histone deacetylase inhibitors in solid tumors.
- Analysis of HDACi's influence on various cancer-related pathways.
- Exploration of combination therapy strategies, including PI3K-EGFR inhibitors, hormone therapy, immunotherapy, bifunctional inhibitors, and PROTACs.
Main Results:
- HDACis demonstrate activity in solid tumors, though further refinement is needed.
- Combination therapies involving HDACis with other targeted agents show potential for increased efficacy.
- Novel approaches like bifunctional inhibitors and PROTACs are emerging for improved HDAC-targeted therapy.
Conclusions:
- HDACis are valuable in cancer therapy, with significant potential in solid tumors.
- Combination strategies are crucial for maximizing the therapeutic benefits of HDACis.
- Emerging technologies like PROTACs offer new avenues for HDAC-targeted cancer treatment.
Related Concept Videos
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:34Inhibition of Cdk Activity
01:27Tumor Immunotherapy
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
02:56Treatment Resistant Cancers