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Epigenetic targets in human neoplasms

Tamer E Fandy1, Steven D Gore

  • 1Division of Hematologic Malignancies, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 1650 Orleans Street, Baltimore, MD 21231, USA.

Epigenomics
|November 30, 2011
PubMed

Insights

Epigenetic silencing of genes drives cancer. Reversing this silencing through DNA methylation reversal or targeting histone modifications offers a promising cancer treatment strategy by re-expressing tumor suppressor genes and miRNAs.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Epigenetic silencing of tumor suppressor genes is a hallmark of cancer.
  • Re-expressing these silenced genes is a viable therapeutic strategy.
  • DNA methylation is a key epigenetic mechanism for gene silencing in tumors.

Purpose of the Study:

  • To explore epigenetic modifications as targets for cancer therapy.
  • To investigate the potential of reversing epigenetic silencing for cancer treatment.
  • To highlight the role of DNA methylation, histone modifications, and miRNAs in cancer epigenetics.

Main Methods:

  • Pharmacological and genetic reversal of DNA methylation to induce gene re-expression.
  • Targeting histone acetylation and methylation with small-molecule modulators.
  • Utilizing oligonucleotides to silence aberrantly expressed microRNAs (miRNAs).

Main Results:

  • Reversal of DNA methylation leads to re-expression of silenced genes and proliferation arrest in tumor cells.
  • Small-molecule modulators of histone acetylation and methylation are in clinical development.
  • Epigenetic deregulation of miRNAs contributes to cancer development and progression, with potential for therapeutic intervention.

Conclusions:

  • Epigenetic therapy, targeting DNA methylation, histone modifications, and miRNAs, holds significant promise for cancer treatment.
  • Combination therapy with different epigenetic modifiers requires further evaluation and optimization.
  • Developing effective epigenetic therapies is crucial for advancing cancer treatment strategies.

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