About 15 children a year in the Netherlands are diagnosed with osteosarcoma. It is the most common bone tumor in childhood. Despite treatments with chemotherapy and surgery, the disease returns in more than one in three children. These children are more difficult to cure. More research into better treatments for osteosarcomas is therefore important.
Risk groups
Biomarkers are characteristics of tumor cells that say something about, for example, the exact diagnosis, or how fast the tumor is growing. Such biological clues help provide each child with the most appropriate treatment. In a new study, published today in JCO Precision Oncology, researchers from the Princess Máxima Center and the Institut Gustave Roussy in Paris, share two new biomarkers that may lead to more personalized treatment for children with osteosarcoma. The research was made financially possible partly through the Princess Máxima Center Foundation.
G2 and MYC
The biomarkers were found thanks to data in the Máxima's biobank. Using two techniques, RNA sequencing and whole exome sequencing, the researchers read out the genetic code of the tumor cells. They linked this DNA and RNA information to the child's disease course. The analysis revealed two genetic changes that can predict a poor prognosis: the so-called G2 RNA expression profile and increased expression of the MYC gene.
Dr. Laura Hiemcke-Jiwa, pathologist in the Laboratory for childhood cancer pathology at the Máxima Center: 'In the case of children with osteosarcoma, the two biomarkers we discovered at diagnosis help to link tumor type to prognosis. In this way, we hope to be able to classify every child into a risk group in future studies.'
Roelof van Ewijk, pediatric oncologist, adds, ‘All children with osteosarcoma are now treated with the same chemotherapy. So, it is very important that with these new biomarkers we can better tailor clinical trials to the individual child. We want to be able to offer each child the best suited treatment. We hope to understand through this study which tumors we may be able to treat with less chemotherapy or where we need new forms of treatment. This is important for children who are currently being treated for osteosarcoma, as well as for the development of new treatments.’
Step closer to clinical practice
Van Ewijk and Hiemcke-Jiwa examined tumor cells from 48 children with osteosarcoma treated at the Máxima between 2018 and 2023. They did this under the guidance of associate research group leader Dr. Lennart Kester and Dr. Antonin Marchais who leads osteosarcoma research at the Gustave Roussy Insitute in Paris. Kester: ‘The two biomarkers had already been found in previous research, including from Marchais. With this study, thanks to the tumor cells from these 48 children, we have validated, or demonstrated, that the biomarkers are linked to a worse prognosis. It is nice to use our research to bring the biological invention in the lab one step closer to clinical practice.’
Follow-up research
International follow-up research is needed to make the two biomarkers actually applicable. Kester: ‘We need to examine tumor cells from a larger number of children to be able to determine the two biomarkers with absolute certainty.’ The researchers are collaborating with scientists within the European osteosarcoma consortium (FOSTER). Van Ewijk: 'We would like to investigate the biomarkers in an upcoming large clinical phase III study. By doing so, we will learn better what exactly these biomarkers mean. It will also clarify whether they can really predict the response to medication in a larger group of children. In this way, we hope to be able to treat children with osteosarcoma more effectively and increase the chance of cure with optimal quality of life.'