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 has been 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.

How could this research benefit primary bone cancer patients?

The ultimate goal of this research is to accurately identify differences between Ewing sarcoma and osteosarcoma bulk tumour cells and their circulating equivalents. The differences in these “middle men” of the spread process will provide vulnerabilities of the diseases that can be targeted therapeutically. More widely, this work will inform other research studies, research groups and future clinical trials by identifying specific cellular features that may increase treatment effectiveness.

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