SIP Series - Jessamy Tiffen
Topic: Exploring the Epigenetic Modifier EZH2 as a Driver and Drug Target in Melanoma.
Despite major advances in immunotherapy and targeted therapies for metastatic melanoma, not all patients respond to such treatments and the development of therapy resistance remain key obstacles. Novel targets are required and the epigenetic modifier EZH2 may represent such a solution.
EZH2 methylates histones causing chromatin compaction and silencing of gene expression. Aberrant EZH2 in cancer results in the silencing of hundreds of tumour suppressor genes that would normally constrain cancer growth, and 26% of patients in the Australian Melanoma Genome Project (AMGP) display such abnormal EZH2.
In the following talk I will present evidence, using both in vitro and in vivo mouse melanoma models, that inhibiting EZH2 is a promising therapeutic strategy for melanoma treatment. Using techniques such as ChIP-seq and expression arrays, we identify the downstream EZH2 target genes that may drive melanoma progression. We show these target genes play diverse tumour suppressive roles including differentiation, cell death and the anti-tumour immune response.
Clinical development of EZH2 inhibitors (EZH2i) is underway with >10 active trials for a range of EZH2i compounds, however these phase 1/2 trials do not target melanoma. Our studies suggest that melanoma patients with aberrant EZH2 activity may also benefit from such drugs.
About the speaker
Dr Jessamy Tiffen
Jessamy completed her PhD in Cancer Genetics in 2011 from Sydney University. She conducted post-doctoral training at the Sanger Institute in Cambridge under the guidance of Dr David Adams, where she became interested in the genetics of Melanoma. She is currently a Senior Research Officer in Professor Peter Hersey's laboratory at the Centenary Institute, with a special focus on Epigenetic regulators in Melanoma. She has published in Nature Genetics, Cancer Research and JNCI and currently holds a CIA grant from the Cancer Council of NSW.