Organoids as a new approach for improving pediatric cancer research

Abstract

A key challenge in cancer research is the meticulous development of models that faithfully emulates the intricacies of the patient scenario, with emphasis on preserving intra-tumoral heterogeneity and the dynamic milieu of the tumor microenvironment (TME). Organoids emerge as promising tool in new drug development, drug screening and precision medicine. Despite advances in the diagnoses and treatment of pediatric cancers, certain tumor subtypes persist in yielding unfavorable prognoses. Moreover, the prognosis for a significant portion of children experiencing disease relapse is dismal. To improve pediatric outcome many groups are focusing on the development of precision medicine approach. In this review, we summarize the current knowledge about using organoid system as model in preclinical and clinical solid-pediatric cancer. Since organoids retain the pivotal characteristics of primary parent tumors, they exert great potential in discovering novel tumor biomarkers, exploring drug-resistance mechanism and predicting tumor responses to chemotherapy, targeted therapy and immunotherapies. We also examine both the potential opportunities and existing challenges inherent organoids, hoping to point out the direction for future organoid development.

Keywords: 3D models; cancer modeling; pediatric cancer; precision medicine; tumor organoids.

Figure 1

Simplified sketch illustrating the comparison between conventional 2D cell culture and 3D cell culture, after biopsy collection from the patient tissue. In the accompanying diagram, we illustrate the distinct features and fate of cells cultivated in these two modes. The 2D culture depicts traditional flat monolayers, while the 3D culture showcases a more physiologically relevant three-dimensional arrangement, providing insights into the cellular behavior and potential therapeutic applications.

Figure 2

Potential application of organoids in pediatric cancer research. PDOs can be used for different biomedical applications such as Basic Research and disease modeling, Drug Screening and Drug Development, Biobanking Personalized Medicine and Regenerative Medicine.