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Epigenetic Therapy for Solid Tumors: Highlighting the Impact of Tumor Hypoxia

Epigenetic Therapy for Solid Tumors: Highlighting the Impact of Tumor Hypoxia

Authors :
Adam J. Krieg
Ester M. Hammond
Shaliny Ramachandran
Eva-Leonne Göttgens
Jonathan Ient
Source :
Genes, Genes, Vol 6, Iss 4, Pp 935-956 (2015)
Publication Year :
2015
Publisher :
MDPI AG, 2015.

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.

Details

ISSN :
20734425
Volume :
6
Database :
OpenAIRE
Journal :
Genes
Accession number :
edsair.doi.dedup.....755e71a813291b955356c4443d29d5a6
Full Text :
https://doi.org/10.3390/genes6040935