Ewing sarcoma and osteosarcoma are the most common types of primary bone cancer diagnosed in children, teenagers and young adults. A major challenge when treating patients with Ewing sarcoma and osteosarcoma is the possibility of metastasis. Metastasis occurs when cancer cells escape from the original (i.e. "primary”) tumour and travel via the bloodstream to distant tissues (usually the lungs or bone marrow) where they are able to settle and thrive, giving rise to new, secondary tumours.
Slowing down metastasis, or stopping it altogether, is a major aim of the research group of Dr Darrell Green at the University of East Anglia.
The team of researchers have recently shown that primary and secondary tumours are not overly dissimilar in terms of the genes that they express, so it is difficult to pinpoint the key molecular processes that underly metastasis.
Interestingly, cancer cells in the blood that have escaped the primary tumour (called “circulating tumour cells”) appear to be very different to those cancer cells present in both primary and secondary tumours.
Their initial data suggests that circulating tumour cells express ‘new’ genes that enable them to survive their journey from the primary site and complete the process of metastasis. It is hypothesised that whilst these new genes may help the cancer to spread, they provide an “Achilles heel” that can be exploited therapeutically to stop metastasis in its tracks.
What are the aims of this research project?
Tumours may be detected by CT scans when they are just 2-3 mm in size, whilst this is small, they are already composed of an ‘ecosystem’ of tens of millions of cancer cells.
Although we know that the cancer cells making up the bulk of the tumour are quite different from each other; normally, work performed in the laboratory takes an average account of the molecules that are present and the genes that are expressed in a whole tumour.
To accurately determine how different circulating tumour cells are from those in primary and secondary tumours (bulk tumour cells), we need to characterise them individually.
An Ideas Grant was awarded to the group to individually characterise cancer cells isolated from Ewing sarcoma and osteosarcoma patients’ samples, so their individual and unique properties may be more clearly understood and used as more appropriate controls. This information will be essential for their own research, but will also be made available to other researchers, enriching the value of the knowledge acquired by paving the way towards other potential future advancements across the field of primary bone cancer research.
FINDINGS
The researchers looked at patient-derived metastatic cells (circulating tumour cells (CTCs)) and compared the gene expression of these cells using a technique called ‘single-cell RNA sequencing which allows the study of single cells within their tumour microenvironment, to that of normal cells and other cancer cells that have not metastasised. The findings from the research showed that the metastatic cells accessed specific genes in their DNA that normal cells and even tumour cells that have not metastasised cannot. They found that metastasised-related transcripts which are molecules that are expressed in cancer, were absent or under-expressed in non-metastatic tumour cells but overexpressed in metastatic cells.
CONCLUSIONS AND OUTCOMES FOR PATIENTS
This research has shown that metastatic cells from paediatric bone sarcomas do not follow the same genetic pattern seen in adult cancers. The researchers concluded that this finding is important, because it means that ‘metastasis specific genes’ exist, which means potential future treatments can be developed to ‘attack’ these genes without harming normal cells.
FUTURE PLANS
The research has been published: Bull et al. Molecular Cancer (2025) 24:153
https://doi.org/10.1186/s12943-025-02365-z
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