Research part-funded by the Bone Cancer Research Trust has shown how the microenvironment surrounding a Giant Cell Tumour of the Bone interacts with Denosumab – the most popular drug used to treat the disease.

Leading researchers from the UK and Germany came together to examine activity around the tumour site and how it changes when the tumour is treated with Denosumab.

The environment surrounding a Giant Cell Tumour of the Bone is dominated by bone-destroying cells known as osteoclasts. In this rare tumour type, the osteoclasts are abnormally large. This is important to how Denosumab treats the tumour as it works by blocking their formation, directly impacting the tumour microenvironment.

The study also demonstrated how a Giant Cell Tumour of the Bone forms, which involves miscommunication between bone-forming cells and cells that break down the bone.

To enable this research, patient samples were collected through the Royal National Orthopaedic Hospital (RNOH), a national sarcoma centre that is funded by the Bone Cancer Research Trust's Infrastructure Grants.

How does a Giant Cell Tumour of the Bone form?

Mesenchymal cells can self-renew and develop into different cell types, including osteoclasts or 'bone-destroying cells.' Changes to mesenchymal cells caused by the H3.3-G34W mutation results in an increased number of osteoclasts.

Osteoclasts in turn produce a protein called SEMA4D, which enhances the spread of mutated bone-forming cells and results in a Giant Cell Tumour of the Bone.

Denosumab works by reducing the number of osteoclasts within the tumour. A different mutation, known as the hTERT alteration that is found in a cancerous Giant Cell Tumour of the Bone, results in mutated tumour cells which are not reliant on osteoclasts to grow. This explains why a malignant Giant Cell Tumour of the Bone is unresponsive to Denosumab.

The study has been published in the Cell Death & Differentiation journal and is freely available here.