Epigenetics

A critical change in the multistage process of tumorigenesis is selection for an aberrant epigenetic code that does not involve a change in DNA sequence, but results in a stable change in gene expression. All tumor types show aberrant regulation of the epigenome, including changes in DNA methylation, histone modification and microRNAs.

In the Epigenetics Unit we are examining changes in the cancer epigenome to provide understanding of tumour development and progression, including the acquisition of drug resistance during treatment. These changes provide diagnostic, prognostic and predictive biomarkers for improving clinical management of patients.

As an example, we have shown that DNA methylation at particular genes involved in DNA repair or cell signaling pathways predict survival of ovarian cancer patients following platinum-based chemotherapy. We are then using these biomarkers for patient stratification in clinical trials of novel epigenetic therapies such as demethylating agents. We also are characterizing these epigenetic changes in detail as potential targets for development of novel therapies, particularly in important subpopulations of tumour cells, such as drug resistant and tumour stem cells.

Working closely with drug development chemists and oncologists we are translating these findings into clinical trials that use epigenetic biomarkers to tailor treatments to the most appropriate patients.