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Published on: April 5, 2018
Progress Toward Epigenetic Targeted Therapies for Childhood Cancer
Athanasia Liapodimitri1, Ashley R Tetens1, Jordyn Craig-Schwartz1
1Division of Pediatric Oncology, Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA.
Abstract:
Among the most significant discoveries from cancer genomics efforts has been the critical role of epigenetic dysregulation in cancer development and progression. Studies across diverse cancer types have revealed frequent mutations in genes encoding epigenetic regulators, alterations in DNA methylation and histone modifications, and a dramatic reorganization of chromatin structure. Epigenetic changes are especially relevant to pediatric cancers, which are often characterized by a low rate of genetic mutations. The inherent reversibility of epigenetic lesions has led to an intense interest in the development of epigenetic targeted therapies. Additionally, the recent appreciation of the interplay between the epigenome and immune regulation has sparked interest in combination therapies and synergistic immunotherapy approaches. Further, the recent appreciation of epigenetic variability as a driving force in cancer evolution has suggested new roles for epigenetic therapies in limiting plasticity and resistance. Here, we review recent progress and emerging directions in the development of epigenetic targeted therapeutics and their promise across the landscape of childhood cancers.
Insights
Epigenetic dysregulation is key in cancer, especially pediatric types. Reversible epigenetic therapies offer new treatment strategies and can be combined with immunotherapy.
Area of Science:
- Oncology
- Genetics
- Epigenetics
Background:
- Epigenetic dysregulation is a significant factor in cancer development and progression.
- Alterations in DNA methylation, histone modifications, and chromatin structure are common in various cancers.
- Epigenetic changes are particularly relevant in pediatric cancers due to their low mutation rates.
Purpose of the Study:
- To review recent advancements in epigenetic targeted therapeutics for childhood cancers.
- To explore emerging directions in epigenetic therapy development.
- To highlight the potential of epigenetic therapies in combination with immunotherapy.
Main Methods:
- Review of current literature on epigenetic dysregulation in cancer.
- Analysis of studies on epigenetic targeted therapies.
- Examination of research on epigenome-immune interactions.
- Investigation of epigenetic variability in cancer evolution.
Main Results:
- Frequent mutations in epigenetic regulators and altered epigenetic marks are observed across cancer types.
- The reversibility of epigenetic lesions fuels interest in targeted epigenetic therapies.
- The interplay between epigenome and immune regulation suggests synergistic immunotherapy approaches.
- Epigenetic variability drives cancer evolution, suggesting new therapeutic roles.
Conclusions:
- Epigenetic targeted therapeutics show promise for childhood cancers.
- Combination therapies involving epigenetic agents and immunotherapy are a growing area of interest.
- Epigenetic therapies may help limit cancer plasticity and resistance.
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