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Updated: Apr 13, 2026

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Epigenetic therapy for solid tumors: from bench science to clinical trials
Yen-Yi Juo1, Xue-Jun Gong, Ankita Mishra
1Department of Surgery, George Washington University Medical Center, 2150 Pennsylvania Ave. NW, Suite 6B, Washington, DC 20037, USA.
Abstract:
The cancer epigenome is characterized by global DNA methylation and chromatin changes, such as the hypermethylation of specific CpG island promoters. Epigenetic agents like DNA methyltransferase or histone deacetylase inhibitors induce phenotype changes by reactivation of epigenetically silenced tumor suppressor genes. Despite initial promise in hematologic malignancies, epigenetic agents have not shown significant efficacy as monotherapy against solid tumors. Recent trials showed that epigenetic agents exert favorable modifier effects when combined with chemotherapy, hormonal therapy, or other epigenetic agents. Due to the novel nature of their mechanism, it is important to reconsider the optimal patient selection, drug regimen, study design, and outcome measures when pursuing future trials in order to discover the full potential of this new therapeutic modality.
Insights
Epigenetic agents can reactivate silenced tumor suppressor genes in cancer. While not effective alone in solid tumors, they show promise when combined with other cancer treatments.
Area of Science:
- Oncology
- Cancer Epigenetics
- Molecular Biology
Background:
- The cancer epigenome exhibits global DNA methylation and chromatin alterations, including CpG island promoter hypermethylation.
- Epigenetic agents, such as DNA methyltransferase and histone deacetylase inhibitors, aim to reverse these changes by reactivating silenced tumor suppressor genes.
Purpose of the Study:
- To review the efficacy of epigenetic agents in cancer therapy.
- To explore the potential of combining epigenetic agents with other treatment modalities.
- To suggest optimal strategies for future clinical trials involving epigenetic agents.
Main Methods:
- Review of existing clinical trial data and scientific literature on epigenetic agents in cancer.
- Analysis of combination therapy outcomes involving epigenetic agents, chemotherapy, and hormonal therapy.
- Discussion of novel therapeutic strategies and trial designs for epigenetic agents.
Main Results:
- Epigenetic agents have shown limited efficacy as monotherapy in solid tumors.
- Combinations of epigenetic agents with chemotherapy, hormonal therapy, or other epigenetic agents demonstrate favorable modifier effects.
- These agents can induce phenotypic changes by reactivating epigenetically silenced tumor suppressor genes.
Conclusions:
- Epigenetic agents hold promise as combination therapy for solid tumors, rather than monotherapy.
- Future research should focus on optimizing patient selection, drug regimens, study designs, and outcome measures.
- Unlocking the full therapeutic potential of epigenetic agents requires a strategic approach to clinical development.
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