| Popis: |
Pediatric renal tumors are among the most frequent malignancies in children. The majority of patients is diagnosed with Wilms tumors. While survival rates have reached 90%, patients still suffer from severe long-term side effects, caused by the harsh therapy regiments. Furthermore, patients affected by rarer renal tumor subtypes, such as malignant rhabdoid tumor of the kidney (MRTK) and recurrent relapsed Wilms tumor (RWT), carry a dismal prognosis. To improve survival rates and quality of life for pediatric renal tumor patients, alternative therapies need to be sought. In recent years therapeutic innovation has been impaired by different factors, including the lack of preclinical models able to closely represent characteristics of pediatric kidney tumors. New frontiers in cell culture techniques allow for the establishment and expansion of multicellular structures, derived from stem cells, that self-organize to grow in a 3D fashion. These “mini organs”, able to mimic the architecture – and partial function - of the original tissues, are named organoids. Organoids can be generated from healthy tissues as well as from tumors. Tumor organoids can be established with high efficiency from patient tumor material, while maintaining characteristics of the original tissue, such as histology and genetic makeup. Furthermore, several studies have shown that tumor organoids are able to mirror the response to therapy registered in patients, making them appealing models for drug screening purposes. In this thesis, we present for the first time the application of the organoid technology to pediatric cancer research. We successfully generated more than 50 unique patient-derived organoid cultures for which preclinical models were scarce. This collection of organoids provides with the opportunity to study these rare malignancies with the advantages of an in vitro model, while the characteristics of the original tumors are still recapitulated to a large extend. We demonstrate that it is feasible to use these models to perform drug screening and identify novel therapy for high-risk pediatric patients. The work presented in this thesis sets the first steps towards the implementation of the organoid technology as tool for improving treatment of children with cancer. |
