- SCCOHT organoids have been grown in the lab for the first time
- Drug screening with organoids indicate methotrexate as an effective and selective candidate for the treatment of SCCOHT
- Future studies and discussions are needed to determine whether methotrexate can become a standard part of therapy for these children
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a very rare form of childhood cancer that occurs in girls and young women. Only a few children with SCCOHT have been treated for this since the opening of the Princess Máxima Center. No standard treatment is currently in place, and the cure rate is low at 10 to 20%. Research into new, better treatments is therefore important. But because of the very limited research material, this has previously been difficult.
In search of an effective drug
Researchers from the Clevers group e.t. at the Princess Máxima Center have succeeded in growing SCCOHT organoids. This allowed them to test the effect of 153 pediatric oncology drugs on tumor cells. From the tests, methotrexate appeared as an effective and selective drug.
Today, the results of the study led by Prof. Dr. Hans Clevers, former research group leader at the Princess Máxima Center and Oncode Investigator, were published in Science Advances. Stichting Kinderen Kankervrij (KiKa), Oncode Institute and Oncode Accelerator made this research possible.
The SCCOHT organoids are a good example of the type of organoids that will be included in the Central Máxima Organoid Biobank (CMOB). These organoids can eventually be requested by researchers from both inside as well as outside the Máxima, which will increase and improve pediatric cancer research worldwide.
Recapulating
The researchers used tumor material from three children with SCCOHT to grow mini tumors in the lab. This tumor material came from the biobank of the Máxima. Seok-Young Kim, PhD candidate in the Clevers group e.t. and first author succeeded together with his colleagues in growing the organoids. He says: ‘We were able to culture eight different organoid lines from the eight tumor samples available in the biobank. These were from three children. Analyses show that the cultured organoids reflect the original tumor tissue, both on a genetic and transcriptomic level.'
In the high-throughput screening facility at the Máxima Center, the organoids were then exposed to 153 different active substances from drugs already used within pediatric oncology. Kim: ‘We saw that methotrexate was the most effective and selective drug in the library, even when compared to the drugs that are used to treat SCCOHT patients.’
Prof. Dr. Hans Clevers, pioneer in the field of organoids: 'This research shows that organoids can help determine treatment strategies for this and other rare cancers.'
Clinical application
Currently, there is no standard treatment for SCCOHT available. The very small number of patients, children and young adults, makes setting up clinical trials complex.
Dr. Jozsef Zsiros, pediatric oncologist at the Máxima Center and involved in the study: ‘The results in the lab are very promising. Together with colleagues from other research hospitals, I will discuss the next steps for clinical application to determine whether methotrexate can become a standard part of therapy. Because methotrexate is already used in pediatric oncology and the survival rate of SCCOHT patients is low, we will assess, for example, whether methotrexate is appropriate on a child-by-child basis. This way we would learn whether this finding can increase the survival rate of this rare, aggressive ovarian cancer.'