Epigenetic therapy for solid tumors: Highlighting the impact of tumor hypoxia

Shaliny Ramachandran, Jonathan Ient, Eva Leonne Göttgen, Adam Krieg, Ester M. Hammond

Research output: Contribution to journalReview article

22 Citations (Scopus)

Abstract

In the last few decades, epigenetics has emerged as an exciting new field in development and disease, with a more recent focus towards cancer. Epigenetics has classically referred to heritable patterns of gene expression, primarily mediated through DNA methylation patterns. More recently, it has come to include the reversible chemical modification of histones and DNA that dictate gene expression patterns. Both the epigenetic up-regulation of oncogenes and downregulation of tumor suppressors have been shown to drive tumor development. Current clinical trials for cancer therapy include pharmacological inhibition of DNA methylation and histone deacetylation, with the aim of reversing these cancer-promoting epigenetic changes. However, the DNA methyltransferase and histone deacetylase inhibitors have met with less than promising results in the treatment of solid tumors. Regions of hypoxia are a common occurrence in solid tumors. Tumor hypoxia is associated with increased aggressiveness and therapy resistance, and importantly, hypoxic tumor cells have a distinct epigenetic profile. In this review, we provide a summary of the recent clinical trials using epigenetic drugs in solid tumors, discuss the hypoxia-induced epigenetic changes and highlight the importance of testing the epigenetic drugs for efficacy against the most aggressive hypoxic fraction of the tumor in future preclinical testing.

Original languageEnglish (US)
Pages (from-to)935-956
Number of pages22
JournalGenes
Volume6
Issue number4
DOIs
StatePublished - Sep 25 2015
Externally publishedYes

Fingerprint

Epigenomics
Neoplasms
Therapeutics
DNA Methylation
Histone Code
Clinical Trials
Gene Expression
Tumor Hypoxia
Histone Deacetylase Inhibitors
DNA
Methyltransferases
Oncogenes
Pharmaceutical Preparations
Histones
Up-Regulation
Down-Regulation
Pharmacology

Keywords

  • DNA methylation
  • Epigenetic drugs
  • Gene-repression
  • Histone deacetylation
  • Histone methylation
  • Tumor hypoxia

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Ramachandran, S., Ient, J., Göttgen, E. L., Krieg, A., & Hammond, E. M. (2015). Epigenetic therapy for solid tumors: Highlighting the impact of tumor hypoxia. Genes, 6(4), 935-956. https://doi.org/10.3390/genes6040935

Epigenetic therapy for solid tumors : Highlighting the impact of tumor hypoxia. / Ramachandran, Shaliny; Ient, Jonathan; Göttgen, Eva Leonne; Krieg, Adam; Hammond, Ester M.

In: Genes, Vol. 6, No. 4, 25.09.2015, p. 935-956.

Research output: Contribution to journalReview article

Ramachandran, S, Ient, J, Göttgen, EL, Krieg, A & Hammond, EM 2015, 'Epigenetic therapy for solid tumors: Highlighting the impact of tumor hypoxia', Genes, vol. 6, no. 4, pp. 935-956. https://doi.org/10.3390/genes6040935
Ramachandran, Shaliny ; Ient, Jonathan ; Göttgen, Eva Leonne ; Krieg, Adam ; Hammond, Ester M. / Epigenetic therapy for solid tumors : Highlighting the impact of tumor hypoxia. In: Genes. 2015 ; Vol. 6, No. 4. pp. 935-956.
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