2022 New Investigator Grant

Orazio Vittorio, Recipient

University of New South Wales

Exploring copper chelation as a novel epigenetic therapeutic strategy for DIPG

Abstract:

Brain cancers are the leading cause of disease-related death and burden in children across the USA, Europe, and Australia. They are known to be difficult to treat, and even in ones where there is long-term survival, many kids suffer from infertility, the onset of adult cancers, and in many cases psychiatric illnesses which result in depression and suicide. With this in mind, there is now an active focus on novel drug combinations, aimed at not only improving survival, but improving the quality of life for these patients after treatment. One of the children’s brain cancers we are aiming to cure is Diffuse Intrinsic Pontine Glioma (DIPG), a devastatingly aggressive cancer with universal death, with all patients dying within 2 years of diagnosis. This cancer is defined by epigenetic mutations, with many clinical drug trials focusing on targeting these epigenetic mechanisms. However, a cure has not yet been found. Our group works with copper chelating agents, which already have wide use in other cancers, and importantly in children treating epilepsy and genetic diseases resulting in excess copper accumulation, demonstrating the efficacy of these agents in penetrating, and treating the brain with low toxicity. Our evidence indicates that these agents also target epigenetic mechanisms, and with its established positive profile, we believe that these copper chelators can be accelerated faster into clinical trial alongside other epigenetic targeting drugs and help these children. This grant will allow our research group to exercise our expertise in copper biology, further uncovering the epigenetic and metabolic underpinnings of DIPG and its aggressive nature, with our end goal to develop a novel drug combination strategy killing these cancer cells by reducing their copper and impairing their epigenetic mutations with a low risk of side effects, improving not only their survival rate but their quality of life moving forward.