Abstract IA012: Modelling childhood cancer using organoid technology

Abstract

Cancer is still one of the leading causes of disease-related deaths in children. Survivors suffer from side effects of the, in most cases, intensive treatment regimens. Hence, there is an urgent need to develop improved, less toxic therapies. Our vision is that if we understand the processes that underpin the development of childhood cancer, we will facilitate improved cure rates and a better quality of life. However, therapeutic innovation is hampered by the lack of cell models representative of native tumor tissue. The organoid technology has revolutionized cancer research, as it allows for the ‘unlimited’ expansion of healthy and diseased tissue from individual patients in a dish, while retaining essential characteristics of native tissue. Organoids are therefore seen as avatars of the tissues they were derived from (Drost & Clevers, Nat Rev Cancer 2018). We recently succeeded in establishing culture protocols to grow organoids from a wide spectrum of pediatric malignancies such as Wilms tumors, renal cell carcinomas, as well as different rhabdoid tumor and soft tissue sarcoma subtypes. Subjecting our models to a comprehensive molecular profiling, we were able to demonstrate that pediatric cancer organoids retain many features of the tissues they were derived from (Calandrini et al., Nat Commun 2020; Calandrini et al., Cell Rep 2021; Meister et al., EMBO Mol Med 2022; Paassen et al., Oncogene 2023). Thus, we massively expanded the number of relevant pre-clinical in vitro model systems for cancers for which models were rare or even non-existing, including different pediatric kidney cancer subtypes. We use these models in combination with genetic engineering and (single-cell) omics technologies to study the very fundamental processes underlying tumorigenesis with the aim to find new therapies.

Citation Format: Jarno Drost. Modelling childhood cancer using organoid technology [abstract]. In: Proceedings of the AACR Special Conference: Advances in Kidney Cancer Research; 2023 Jun 24-27; Austin, Texas. Philadelphia (PA): AACR; Cancer Res 2023;83(16 Suppl):Abstract nr IA012.