Ron Firestein Lab
Cancer Genetics and Functional Genomics
PROJECT 2: Targeting the Epigenetic Regulators in Colon Cancer
Therapeutic Targeting of the Colon Cancer Epigenome
Colorectal cancer (CRC) is the second most common malignancy in Australia with over 17,000 cases diagnosed a year. Recent analyses have uncovered epigenetic alterations as major drivers of tumourigenesis in CRC. With the emergence of epigenetic targeted therapeutics, it is now clear that DNA methylation and histone modification are reversible processes that can be targeted for intervention using small molecule inhibitors of epigenetic writers (methyltransferases, acetyltransferases, kinases), readers (bromodomain- or chromodomain-containing genes) and erasers (demethylases, deacetylases, phosphatases). This project uses genome editing technology to target nearly ~1000 epigenetic regulators and dissect their involvement in regulating key oncogenic signalling pathways such as Wnt/b-catenin and expression of critical oncogenes such as c-MYC.