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New research model: mini-tumors of the kidney

Kidney tumors represent the second most common solid malignancy in children. The diversity is great; whereas the most common  kidney tumor, Wilms tumor, is generally well treatable, the prognoses for non-Wilms tumors is much poorer. The last years little progress has been made in the development of new, less toxic treatment options. This is partly caused by the lack of representative models that can be used for research purposes. The group of Jarno Drost at the Princess Máxima Center for pediatric oncology succeeded in establishing organoid cultures (mini-tumors) derived from a variety of different childhood kidney tumors spectrum, which can be used to study the biology of these tumors as well as to test new medication.

Organoid of a Wilms tumor (credits: Ravian van Ineveld - Rios Group)

 

All children with cancer in the Netherlands are treated In the Princess Máxima Center for pediatric oncology. As part of the treatment, (part of) the tumor is typically resected or a biopsy is taken for diagnostic purposes. The tumor tissue that remains is used for scientific research, provided that the parents consent.  ‘That is a of course a difficult question for parents since they do not know what kind of research is actually performed with the tissue’, says Jarno Drost. ‘Our research demonstrates how valuable the material is for the generation of new research models of relatively rare tumors.’

‘The mini-tumors, or organoids, that we are now able to culture, are very similar to the tumor of the child’, explains Drost. The use of these mini-tumors may provide new insights in the origin of the tumor and the development of novel treatment.

Team sport

The devil is in the details if it comes to culturing mini-tumors in the laboratory. ‘A lot of knowledge and skills have to come together to succeed’, says Drost. The temperature, composition of the air and growth medium have to be fine tuned to mimic the situation in the body. Only then the tissue can be kept alive as an organoid.

The findings of the research, performed by a team consisting of researchers and clinicians from the Princess Máxima Center, Hubrecht Institute, Oncode Institute and UMC Utrecht and supported by the Dutch Cancer Society and KiKa are published in Nature Communications.

Mini-tumors as model

The mini-tumors serve amongst others as model for testing drugs. Under the right circumstances, the Drost group now has an infinite amount of tumor cells to test the sensitivity of the tumor to large collections of medications and combinations.

In addition, the mini-tumors offer the opportunity to study the biology of the tumor in detail. ‘If we can figure out what makes a cell  become malignant we might be able to find new therapeutic targets that specifically kill tumor cells and leave healthy cells unharmed’, he explains.