Professor Agamemnon Grigoriadis explains more about the aims of the new osteosarcoma research project and the difference his research could make for future patients.
Can you tell us a bit about yourself, the project and its aims?
My scientific career has always been focussed on investigating the skeleton, understanding how it forms, what controls the cells that make and destroy our bones during normal life, and how these control mechanisms are altered in disease. Following my PhD studies in Toronto, I became interested in skeletal malignancies and osteosarcoma during my postdoc in Vienna where I was involved in creating one of the first preclinical models of osteosarcoma through genetic modification of mice. I still work on this model to this day which has led to the work proposed in this project.
The project follows current exciting developments in the cancer field on trying to find ways to boost the immune system to fight back against the cancer. Tumour growth is largely controlled by interactions between cancer cells and their environment, which contains immune cells called Tumour-Associated Macrophages (TAMs) that can drive and promote malignancy. One of the proteins made by TAMs is Haem Oxygenase-1 (HO-1), an enzyme whose normal function is to control the breakdown of haem, which is produced by the breakdown of haemoglobin but can be toxic at high levels. However, it is also expressed in a variety of cancers with immunosuppressive properties, and the recent exciting work of our collaborator Dr James Arnold here at KCL showing the therapeutic potential of targeting HO-1 in breast cancer led us to investigate HO-1 expression in osteosarcoma. Indeed, our preliminary studies showed that HO-1 was indeed expressed in osteosarcoma TAMs as well as in metastases (secondary cancers) and therefore our aims are to investigate thoroughly the expression of HO-1 and its upstream regulators in osteosarcomas present in our mouse model as well as in human tumours.
What difference could this project make for osteosarcoma patients in the future?
One very exciting aspect of this project is the fact that there is an inhibitor of HO-1, tin mesoporphyrin (SnMP) that is used clinically for the treatment of neonatal jaundice and hyperbilirubinaemia, and our collaborators have shown that SnMP showed therapeutic efficacy in preclinical models of breast cancer. Translation of basic scientific research to the clinic is of course very difficult and must occur in a step-wise fashion, however, the fact that SnMP is already on the market, together with the current excitement in health care in the area of drug repurposing, we are very excited that further research along the lines of this project will provide benefit for osteosarcoma patients.
In the long term could this research project stop metastases?
The process of metastasis is multifactorial and very complex, and there are many different approaches that researchers have taken to identify each discrete step in the metastatic process, as each of these steps would in principle be a potential therapeutic target. Our research project focusses on the role of TAMs and HO-1 in the tumour/metastastic environment, and we feel that the findings will provide a positive case for targeting TAMs in osteosarcoma and osteosarcoma metastasis. However, we should be open to acknowledge and recognise that collaborative efforts will likely be required through the combined strategies of several laboratories to ultimately prevent metastases.
How important is the funding provided by the Bone Cancer Research Trust?
The Bone Cancer Research Trust provides an essential and, I must say, irreplaceable role in funding for primary bone cancer research. The Bone Cancer Research Trust’s funding schemes have grown and expanded significantly over the years which have allowed researchers to pursue original hypothesis-driven research that is not only published in high-impact journals, but that will also aid in acquiring further funding that underpins further translational research. Indeed, the quality of cutting-edge research publications that are directly attributable to Bone Cancer Research Trust funding has moved the field of bone cancer research and therapy forward significantly.
You’ve been successful in receiving grants from us in the past, do you think we are stimulating the bone cancer research community?
I cannot speak highly enough of how significant the Bone Cancer Research Trust has been, and continues to be, in leading the bone cancer research community. I have indeed been funded previously by the Bone Cancer Research Trust which has not only allowed me to pursue novel ideas in a timely fashion, but has been instrumental for advancing the careers of young scientists that might join the bone research community. I’m very happy to be a part of the Bone Cancer Research Trust community that has grown to be a major player in bone cancer research both in the UK and internationally.
What would you say to our supporters who are raising funds for research?
The fundraising efforts of the Bone Cancer Research Trust are second to none largely due to the commitment and enthusiasm of its supporters and fundraisers. Participating in several fundraising exercises myself, I am impressed by how the Bone Cancer Research Trust continues to instil within its supporters a sense of community and a family atmosphere. I have also been very fortunate to meet some of the families and children who are affected by different bone cancers which always provide a constant inspiration.