Background of the research:
Osteosarcoma (OS) is the most common type of primary bone cancer in children and young adults. It can become resistant to conventional therapies and tends to spread (metastasise), particularly to the lung.
Osteosarcoma tumours develop in a favourable microenvironment composed of bone cells, blood vessels, and immune cells. These cells interact with cancer cells and facilitate disease progression, before leaving the bone and migrating to the lung through the bloodstream. “Circulating tumour cells” travelling through the bloodstream could be used as markers (biomarkers) of early cancer spread.
The purpose of this research was to study these circulating tumour cells and the osteosarcoma tumour microenvironment in order to identify novel treatments for advanced disease.
Results of the study:
Pre-chemo osteosarcoma biopsies were used to characterise the bone microenvironment in which the tumour develops, with the aim of identifying new biomarkers linked to tumour dormancy and reactivation.
Two types of potential markers were identified:
- M1 and M2 are immune cells present in high numbers in the microenvironment of solid tumours. The study concluded that the presence of M2 cells is favoured in OS metastatic tissues, whereas M1 cells were more abundant in localised non-metastatic osteosarcoma samples.
- A protein named Interleukin 34, is present at high levels in OS tissue samples and could be used as a marker to predict the course of the disease. In two research animal models, the researchers proved that when this protein is inhibited, a marked reduction on tumour progression was also achieved.
Detection and isolation circulating tumour cells (CTCs).
The researchers detected, isolated and characterised circulating osteosarcoma cells in animal models, these cells can be used as biomarkers to predict early signs of metastatic spread and/or response to treatment.
Circulating tumour cells can be used as predictive biomarkers in patients suffering from osteosarcoma, to identify early relapse and metastatic spread.
By using the experience acquired with the animal research models, the researchers developed the methods for isolating CTCs in patient samples. Their characterisation at the molecular level is now in progress.
By analysing patient samples, the researchers demonstrated that the microenvironment plays a key role in the control of osteosarcoma progression, confirmed this observation in research models and identified potential new therapeutic targets.
Circulating tumour cells (CTCs) are promising biomarkers. The group has set up the procedure for isolating CTCs in patients and now actively contribute to the ICONIC clinical study, for which they oversee the isolation of CTCs in osteosarcoma patients.
Further research will continue to better understand the role of the tumour microenvironment and CTCs in the recurrent disease.