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The promise of epigenetic therapy: reprogramming the cancer epigenome
Andrew D Kelly1, Jean-Pierre J Issa1
1Fels Institute for Cancer Research and Molecular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
Abstract:
Epigenetics refers to heritable molecular determinants of phenotype independent of DNA sequence. Epigenetic features include DNA methylation, histone modifications, non-coding RNAs, and chromatin structure. The epigenetic status of cells plays a crucial role in determining their differentiation state and proper function within multicellular organisms. Disruption of these processes is now understood to be a major contributor to cancer development and progression, and recent efforts have attempted to pharmacologically reverse such altered epigenetics. In this mini-review we introduce the concept of epigenetic drivers of cancer and discuss how aberrant DNA methylation, histone modifications, and chromatin states are being targeted using drugs either in preclinical, or clinical development, and how they fit in the context of existing therapies.
Insights
Epigenetics, heritable changes beyond DNA sequence, influences cell function and cancer. This review explores targeting epigenetic alterations like DNA methylation and histone modifications with new drugs for cancer therapy.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- Epigenetics involves heritable molecular changes that affect phenotype without altering DNA sequence.
- Key epigenetic features include DNA methylation, histone modifications, non-coding RNAs, and chromatin structure.
- Cellular epigenetic status is vital for differentiation and function; its disruption contributes to cancer.
Purpose of the Study:
- To introduce the concept of epigenetic drivers of cancer.
- To discuss the targeting of aberrant epigenetic modifications in cancer drug development.
- To contextualize these emerging therapies within existing cancer treatment strategies.
Main Methods:
- Review of current literature on epigenetic modifications in cancer.
- Analysis of preclinical and clinical drug development targeting epigenetic alterations.
- Synthesis of information on the role of DNA methylation, histone modifications, and chromatin states in cancer.
Main Results:
- Epigenetic alterations are significant contributors to cancer development and progression.
- Numerous drugs targeting aberrant DNA methylation, histone modifications, and chromatin states are in development.
- These epigenetic therapies show potential to complement or enhance existing cancer treatments.
Conclusions:
- Aberrant epigenetic modifications are key drivers in cancer.
- Pharmacological targeting of epigenetic processes represents a promising therapeutic avenue.
- Future cancer therapies will likely integrate epigenetic drugs with conventional treatments.