Epigenetic modifications are changes to the genome that do not involve a change in the nucleotide sequence.1 They are essential for normal development and maintenance of tissue-specific gene expression patterns in mammals.2,3
Epigenetic mechanisms involved in regulating gene expression and chromatin structure in normal mammalian cells include2-4:
Histone post-translational modifications (PTMs) are key regulators of gene expression.4
Global changes in the epigenetic landscape are a hallmark of cancer.2,3
Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation.2,3 Abnormal epigenetic modifications can contribute to tumorigenesis and resistance to cancer therapy by1,3-6:
Pharmacological research in this area focuses on approaches to cancer treatment that include inhibiting the epigenetic mechanisms involved in histone modifications, chromatin remodeling, and transcription regulation.6
Strategies for addressing epigenetic modifications therapeutically include targeting writers, erasers, and readers as well as other pathways that regulate gene expression, such as PARP and BET.2,3
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