Despite an overall improvement in survival in children with cancer, survival rates for those with aggressive cancers, such as high-risk neuroblastoma and brain tumours, remain dismal. Moreover, survivors frequently have life-long health issues due to the toxic effects of chemotherapy. Targeted and less toxic therapies are urgently required.
Our group is investigating the role of metals in cancer prevention and tumour progression. Our current focus is on the element copper (Cu), which is known to occur at high levels in many types of cancers. In particular, we are interested in the role of copper in the growth of neuroblastoma and gliomas (brain cancer).
Through this research, we hope to be able to develop new drug treatments that target the copper in cancer cells. The great benefit of this therapeutic approach is that it specifically targets cancer cells, causing less damage to healthy cells and therefore fewer unwanted side-effects. We are also working on developing copper-based imaging protocols that will allow clinicians to monitor tumour growth and drug response in patients.
Our main objectives are to:
- understand the biology and aggressive behaviour of neuroblastoma and gliomas
- develop therapeutic strategies to specifically target tumour cells in these cancers
- develop imaging protocols to monitor drug responses
Dr Orazio Vittorio
Positron emission tomography (PET) has revolutionised the imaging of cancer by adding functional metabolic information to anatomic imaging data. PET is non-invasive, highly sensitive, and quantitative tomographic imaging. The use of radioactive copper (64Cu) in PET imaging is an attractive method for tumour detection, since it combines the high sensitivity of PET with higher copper uptake specifically in cancer cells.
We have recently demonstrated using PET imaging that 64Cu accumulates in the tumour mass in a pre-clinical model of neuroblastoma. We are continuing our research with the aim of developing clinical translational 64Cu based PET imaging protocols to determine drug resistance, and to monitor tumour progression and treatment response in neuroblastoma.
Dr Orazio Vittorio
With strong evidence that copper levels are significantly elevated in a wide range of tumours, copper is an emerging target for novel therapeutics. It is an essential component in key cellular processes and is required for at least three phenomena characteristic of cancer progression: endless proliferation, angiogenesis (tumour blood supply) and metastasis.
Our research has shown that the expression of copper transporter 1 and the intracellular copper levels in neuroblastoma cells are ~70% and ~50% higher, respectively, than those in non-malignant cells, suggesting copper is a potential target. Our goal in this project is to develop effective cancer treatments that target copper in tumours, using sophisticated new approaches grounded in an ever more detailed understanding of cancer biology.
Dr Orazio Vittorio
We know from our research that the level of copper in neuroblastoma cells is approximately 50% higher than in normal cells, suggesting copper as a potential target for cancer therapeutics. Furthermore, we have discovered that copper is essential for the expression of the immune-checkpoint proteins regulating anti-cancer immune response in neuroblastoma.
Immunotherapy ― treatment aimed at stimulating a patient’s immune system to fight cancer ― has so far not achieved any significant success in improving survival in neuroblastoma. This is because neuroblastoma cells are capable of expressing molecules such as the programmed death ligand 1 (PD-L1) to prevent immune cells from attacking them. This project explores the hypothesises that modulation of copper homeostasis can be harnessed as a key therapeutic strategy for enhancing the anti-tumour immune response by inhibiting PD-L1 expression. Our goal is to develop therapeutic protocols that combine clinically available copper targeting drugs with immunotherapies to improve their efficacy and hence the survival of children with neuroblastoma.
Team LeaderDr Orazio Vittorio
Dr Federica Saletta