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Epigenetics


The promise of epigenetic biomarkers The epigenetics arena has become a rich and excit- ing global research environment, inspiring collabo- rations between commercial and academic part- ners that have identified many significant epigenet- ic biomarkers for a wide range of serious and debilitating diseases14.


Precise mapping and measurement of epigenetic biomarkers will improve clinical practice by enabling diagnosis during early stages of disease development, even before genetic changes have taken place4. Research in glioblastoma shows that epigenetic alterations associated with tumorigenesis can be detected in neighbouring non-tumour cells, even though they appear to be genetically ‘normal’4. Researchers have also demonstrated that epigenetic changes precede common genetic mutations in an in vitro model of lung cancer15. Epigenetic-based diagnostics that can detect early disease signals will provide opportunities for clinical intervention before symptom progression has impacted on quality of


life, when patients are still relatively fit and con- ditions favour treatment success.


Epigenetic biomarkers allow more accurate dis- ease prognosis, particularly in therapeutic areas that are associated with a high degree of variability concerning survival16-18. Further research in glioblastoma and several other cancers shows that levels of 5hmC are important in the regulation of disease-critical genes. Global reduction in 5hmC across the genome is associated with poor clinical outcomes in these patients5.


These highly-specific biomarkers can help to per- sonalise disease management; allowing treatment response to be monitored more precisely and med- ications to be adjusted accordingly to optimise treatment outcomes, reduce adverse side-effects associated with some medicines and encourage the appropriate use of healthcare resources.


Patient-centred diagnostics


Epigenetic biomarkers for disease are stable. They can be mapped and measured effectively using


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6Tahiliani et al. Conversion of 5-methylcytosine to 5- hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 2009;15;324(5929):930-5. 7 Scourzic et al. TET proteins and the control of cytosine demethylation in cancer. Genome Medicine 2015;7:9. 8 Leenen et al. DNA methylation: conducting the orchestra from exposure to phenotype? Clin Epigenetics. 2016;6;8:92. 9 Castillo-Fernandez et al. Epigenetics of discordant monozygotic twins: implications for disease. Genome Med. 2014;31;6(7):60.


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Drug Discovery World Fall 2017


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