Targeting copper homeostasis as a therapeutic strategy for neuroblastoma

A/Prof Orazio’s grant is generously funded by the Melissa Lewis Foundation.

He is a Project Leader at the Children’s Cancer Institute, The University of New South Wales.

A/Prof Orazio Vittorio completed his PhD in Oncology at the University of Pisa in February 2011, during which he was diagnosed with kidney cancer.

“I was lucky the tumour was found when it was small, so my chances of survival were good,” he says.

“It gave me more reasons to put all my efforts into cancer research. In 2011, I became a father and decided to focus my research in finding better cures for childhood tumours like neuroblastoma. Children are our future!”

In 2020, A/Prof Orazio was awarded the NSW Premier’s Award for Outstanding Cancer Research and in 2021, he received the NSW Young Tall Poppy Award.

A world-first breakthrough

In 2022, A/Prof Orazio was awarded an extension grant that enabled him to continue his vital research and work on clinical trials. 

Neuroblastoma is an aggressive childhood brain cancer for which survival rates are poor, despite the use of intensive therapy. In 2020, A/Prof Orazio and his team made a significant breakthrough in neuroblastoma research, discovering that by removing copper from the blood, you can destroy some of the deadliest cancers that are resistant to immunotherapy. These findings were published in ‘Cancer Research’, a prestigious journal of the American Association for Cancer Research. 

A/Prof Orazio and colleagues studied tumour samples from more than 90 patients with neuroblastoma and 90 patients with gliomas. According to A/Prof Orazio, these two cancers express a protein known as PD-L1 as a way to hide from the immune system, explaining why they are so deadly.

By looking at the human biopsies, the researchers found a correlation between high levels of copper and increased expression of PD-L1. The researchers then showed for the first time in trials that copper levels could control the expression of PD-L1 in cancer cells. Therefore, by reducing the levels of copper within the cancer cells, the tumours are no longer able to hide from the immune system and thus the cancer can no longer thrive.

In 2023, A/Prof Orazio received additional funding to continue his research on brain tumours and immunotherapy.

His findings on copper chelation therapy form the foundation of his focus on tumour microenvironment in glioblastoma, yet another deadly brain cancer with a very poor survival rate of less than 5%. He will be investigating new ways to target therapy-resistant cancer cells in glioblastoma through copper chelation, which may resensitise the immune system to develop more effective ways of fighting the tumours. Read more about this research here.

The importance of funding

With the help from generous donations and the support he’s received through Cure Cancer over the last three years, A/Prof Orazio and his team are now working on clinical trials. This breakthrough will offer a more affordable and more accessible treatment than chemotherapy, with less risk of side effects.

Achievements

A/Prof Orazio joined the University of New South Wales in 2013. Here, he was awarded a Vice Chancellor’s Postdoc Research Fellowship to move to Australia and conduct research at the Children's Cancer Institute of Australia under the mentorship of Professor Maria Kavallaris.

In 2013, he was awarded the CINSW Kids’ Cancer Project Award for Outstanding Cancer Research. Successively, he was awarded a highly competitive CINSW Early Career Fellowship (2014-2016) and a CINSW Career Development Fellowship (2017-2019). A/Prof Orazio recently was awarded a prestigious NHMRC Career Development Fellowship (2019-2023) to develop his career and his own group. He has used his funding to expand his research and build a multidisciplinary group composed of biologists, oncologists and chemists, and has built a network of international collaboration between oncologists from the Sydney Children’s Hospital, biologists from Children’s Cancer Institute, and chemists from the Leibniz Institute in Germany.

He has extensive experience in cancer biology, molecular biology and nanomedicine, and his recent investigations are focused on understanding the role of copper metabolism/homeostasis in cancer (Neuroblastoma and Glioma).

He extends thanks to donors and others working on behalf of Cure Cancer.

“Breakthrough research cannot happen without funding. The support I have received from Cure Cancer has been vital in allowing me to achieve success with my novel research project.”

Together, we can cure cancer.

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