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Table 1 Tumourigenic hypoxia related epigenetic changes and potential therapeutic strategies and targets.

From: Suffocating cancer: hypoxia-associated epimutations as targets for cancer therapy

 

Modification observed in hypoxia related tumourigenesis

Therapeutic potential

DNA methylation

Global DNA hypomethylation

• DNMT inhibition in haematological malignancies

• Re-expression of specific tumour suppressor genes (eg. VHL) through decitabine therapy

Histone modification

• Hypoxic regulation of histone demethylase activity

• Up-regulation of HDAC1 and histone methyltransferase

• HDAC inhibitors disrupt HIF through altered transcription and degradation

• Combination of HDAC inhibiton with mTOR inhibition has additive effect in vitro

miRNAs

mi-RNAs associated with diagnosis and prognosis eg mi-210

• Selected hypoxia related

mi-RNA inhibition through

- Anti-miRNA oligonucleotides

- Antagomirs

• Indirect regulation of miRNA through HIF inhibitors