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Published on: July 25, 2020
Epigenetic-based therapies in cancer: progress to date
Sang-Hyun Song1, Sae-Won Han, Yung-Jue Bang
1Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
Abstract:
Epigenetic gene silencing is a hallmark of cancer cells. Two important types of epigenetic changes are DNA methylation and histone modification. These modifications are catalysed by DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), resulting in chromatin structure changes and gene inactivation. Interestingly, inhibition of these enzymes is known to induce differentiation or apoptosis of cancer cells. Therefore, DNMTs and HDACs have become attractive therapeutic targets. In recent years, many different DNMT and HDAC inhibitors have been developed, and multiple molecular mechanisms through which these agents exert anti-cancer effects have been identified. While a large number of clinical trials are ongoing, hypomethylating agents and HDAC inhibitors seem to be promising for treating several types of cancer. Moreover, developing effective strategies of combining epigenetic therapy with conventional chemotherapy will be one of the major challenges in the future. We briefly review current advances in epigenetic therapies with a focus on recently reported clinical trials.
Insights
Epigenetic gene silencing in cancer involves DNA methylation and histone modification. Inhibiting DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) shows promise in cancer therapy, with ongoing clinical trials exploring their effectiveness.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Epigenetic gene silencing, including DNA methylation and histone modification, is a key feature of cancer.
- DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) catalyze these modifications, leading to gene inactivation.
- Inhibition of DNMTs and HDACs can induce cancer cell differentiation or apoptosis, making them attractive therapeutic targets.
Purpose of the Study:
- To review current advances in epigenetic therapies for cancer.
- To focus on recently reported clinical trials involving DNMT and HDAC inhibitors.
- To discuss the therapeutic potential and future challenges of epigenetic cancer treatments.
Main Methods:
- Review of recent clinical trials and molecular mechanisms of epigenetic therapies.
- Focus on hypomethylating agents and HDAC inhibitors.
- Analysis of anti-cancer effects induced by DNMT and HDAC inhibition.
Main Results:
- Numerous DNMT and HDAC inhibitors have been developed, with identified anti-cancer mechanisms.
- Ongoing clinical trials suggest hypomethylating agents and HDAC inhibitors are promising for various cancers.
- Effective combination strategies of epigenetic therapy with conventional chemotherapy represent a future challenge.
Conclusions:
- Epigenetic therapies targeting DNMTs and HDACs are advancing rapidly.
- Clinical trials indicate significant potential for hypomethylating agents and HDAC inhibitors in cancer treatment.
- Future research should focus on optimizing combination therapies for enhanced efficacy.
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