Sarcoma Organoids Help Find Targeted Treatment

Undifferentiated small-cell sarcomas are rare, aggressive tumors. In the Netherlands, approximately 14 children are diagnosed with this condition each year. The tumors, which include Ewing sarcomas and Ewing-like sarcomas such as CIC::DUX4 sarcomas and BCOR-sized sarcomas, emerge in bone or soft tissue and grow rapidly. 

Currently, children with these cancers all receive the same treatment, even though the tumors differ in many ways. For example, in the DNA of the tumor cells, and the tissue in which the tumor develops. Some of these tumors respond well to reasonably well to chemotherapy, but not all variants do. Therefore, more research is important.

Mini-Tumors From Patient Material 

The researchers started a new collection of organoids containing different forms of small-cell sarcomas. These mini-tumors were cultured from tumor tissue from children who are or have been under treatment in the Máxima Center. The biobank contains material from both the original, primary tumors and tumors at disease recurrence. 

Femke Ringnalda, PhD candidate in the Clevers group e.t., set up the biobank together with colleagues. Ringnalda explains: 

More Targeted Drug Testing 

The organoids prove to be very stable in the lab and retain the genetic characteristics of the original tumor. The difference between subtypes also remains readily apparent, both at the genetic and protein levels. As a result, the researchers see that some tumors respond differently to existing drugs. For example, CIC::DUX4 sarcomas are sensitive to drugs that inhibit the protein MCL-1. These drugs are now rarely used in children with this type of cancer.  

Dr. Karin Sanders, acting research group leader in the Clevers group e.t. and co-lead of this study, says:  "This shows that there really is room for targeted, personalized treatments. It also emphasizes how important it is to look critically at standard treatments for children, especially when organoid studies show that such a treatment is unlikely to work."

Next Steps 

The researchers published their findings today in Nature Communications and was independently confirmed in a back-to-back publication in Nature Communications from the University Children's Hospital Zurich. 

The research was possible thanks to funding from Stichting Kinderen Kankervrij (KiKa) and Oncode Accelerator. The research was led by Sanders, Dr. Marc van de Wetering, and Prof. Dr. Hans Clevers, former research group leader at the Princess Máxima Center, and Oncode Investigator. Prof. Clevers concludes: 

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Princess Máxima Center

About Princess Máxima Center: 

Around 600 children in the Netherlands get cancer every year, and one in four children who are diagnosed with cancer dies from this illness. When a child is seriously ill with cancer, only one thing comes first: cure. That is why at the Princess Máxima Center for pediatric oncology we work together every day in a groundbreaking and passionate way to improve the survival rate and quality of life of children with cancer. Now, and in the longer term. Because children still have a whole life ahead of them. The Princess Máxima Center is not an ordinary hospital, but a research hospital. All children with cancer in the Netherlands are treated here. This makes the Princess Máxima Center the largest pediatric cancer center in Europe. Over 450 researchers and 900 healthcare professionals work closely with Dutch and international hospitals on better treatments and new perspectives on cures. In this way, we give the child of today the very best care and take important steps to improve the chances of survival for the children who are not yet cured.