Dr Orazio Vittorio
NHMRC CDF Fellow, University of New South Wales; Lowy Cancer Research Centre, UNSW
Given the strong clinical evidence that copper levels are significantly elevated in a wide spectrum of tumours, copper homeostasis is considered as an emerging target for anticancer drug design. There is an increase in the number of clinical trials using copper-targeting drugs for the treatment of tumours, and monitoring copper levels in vivo is therefore of paramount importance when assessing the efficacy of those drugs. To date, no method has been reported to monitor and quantify treatment effects through detecting copper levels in vivo. In this study we demonstrated the ability of our compound Dextran-Catechin to dysregulate copper homeostasis in neuroblastoma cancer cells and we developed a [64Cu] CuCl2-PET preclinical imaging method for assessing the accumulation of copper in tumours and potential alterations of copper homeostasis following anti-copper drug treatment. We established this new method in a preclinical mouse model of neuroblastoma to specifically investigate the effect of a novel copper-targeting drug conjugate, Dextran-Catechin (Vittorio et al. Oncotarget 2016, Yee et al. Nature Sc. Rep. 2017, Parmar et al. Theranostics 2018) on copper homeostasis in tumours.
This study is the first of its type, showing the mechanism by which Dextran-Catechin decreases intracellular copper levels in tumour and, the first study which uses 64Cu-PET imaging to monitor anticancer-treatment effect.
This new PET imaging approach has enormous application in assessing the potential of copper-targeting anticancer therapies, both in preclinical and clinical studies, as well as paving the way for personalized drug response profiles.
Dr Vittorio is a Scientia Fellow and Lecturer at the School of Women’s and Children’s Health UNSW and Project Leader at Children’s Cancer Institute. Dr Vittorio’s recent investigation focused on understanding the role of copper metabolism/ homeostasis in cancer (Neuroblastoma and Glioma). As a result of his success, Dr Vittorio has attracted competitive research funding and established multidisciplinary national and international collaborations. In the last five years he has been awarded highly competitive grants for about 2.5 million dollars as sole CI, which he used to expand his research and build his multidisciplinary group. In 2013 Dr Vittorio was awarded the Cancer Institute NSW Premier’s Awards for Outstanding Cancer Research. As a result of his continued research success he was awarded a highly competitive CINSW Early Career Fellowship (2014-2016) and a NHMRC Career Development Fellowship (2019-2023) to develop his career. Dr Vittorio’s leadership in this fi eld is reflected in 73 career peer-reviewed papers, 6 book chapters and 4 patents. Dr Vittorio is member of the Kids Cancer Alliance and he has established collaborations with oncologists and industry partners to progress his discoveries to the clinic.