Beyond regulations at DNA levels: A review of epigenetic therapeutics targeting cancer stem cells

Cell Prolif. 2021 Feb;54(2):e12963. doi: 10.1111/cpr.12963. Epub 2020 Dec 13.

Abstract

In the past few years, the paramount role of cancer stem cells (CSCs), in terms of cancer initiation, proliferation, metastasis, invasion and chemoresistance, has been revealed by accumulating studies. However, this level of cellular plasticity cannot be entirely explained by genetic mutations. Research on epigenetic modifications as a complementary explanation for the properties of CSCs has been increasing over the past several years. Notably, therapeutic strategies are currently being developed in an effort to reverse aberrant epigenetic alterations using specific chemical inhibitors. In this review, we summarize the current understanding of CSCs and their role in cancer progression, and provide an overview of epigenetic alterations seen in CSCs. Importantly, we focus on primary cancer therapies that target the epigenetic modification of CSCs by the use of specific chemical inhibitors, such as histone deacetylase (HDAC) inhibitors, DNA methyltransferase (DNMT) inhibitors and microRNA-based (miRNA-based) therapeutics.

Keywords: DNA methyltransferase; cancer stem cells; epigenetic therapeutics; histone deacetylase; miRNA.

Publication types

  • Review

MeSH terms

  • Antagomirs / metabolism
  • Antagomirs / pharmacology
  • Antagomirs / therapeutic use
  • DNA (Cytosine-5-)-Methyltransferases / antagonists & inhibitors
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Epigenesis, Genetic*
  • Epithelial-Mesenchymal Transition
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylase Inhibitors / therapeutic use
  • Humans
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Neoplastic Stem Cells / cytology
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism*

Substances

  • Antagomirs
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • MicroRNAs
  • DNA (Cytosine-5-)-Methyltransferases