Related Experiment Video
Updated: Oct 3, 2025
Drug Screening of Primary Patient Derived Tumor Xenografts in Zebrafish
Published on: April 10, 2020
Functional Therapeutic Target Validation Using Pediatric Zebrafish Xenograft Models
Charlotte Gatzweiler1,2,3, Johannes Ridinger1,2, Sonja Herter1,2,4
1Hopp Children's Cancer Center Heidelberg (KiTZ), 69120 Heidelberg, Germany.
Abstract:
The survival rate among children with relapsed tumors remains poor, due to tumor heterogeneity, lack of directly actionable tumor drivers and multidrug resistance. Novel personalized medicine approaches tailored to each tumor are urgently needed to improve cancer treatment. Current pediatric precision oncology platforms, such as the INFORM (INdividualized Therapy FOr Relapsed Malignancies in Childhood) study, reveal that molecular profiling of tumor tissue identifies targets associated with clinical benefit in a subgroup of patients only and should be complemented with functional drug testing. In such an approach, patient-derived tumor cells are exposed to a library of approved oncological drugs in a physiological setting, e.g., in the form of animal avatars injected with patient tumor cells. We used molecularly fully characterized tumor samples from the INFORM study to compare drug screen results of individual patient-derived cell models in functional assays: (i) patient-derived spheroid cultures within a few days after tumor dissociation; (ii) tumor cells reisolated from the corresponding mouse PDX; (iii) corresponding long-term organoid-like cultures and (iv) drug evaluation with the corresponding zebrafish PDX (zPDX) model. Each model had its advantage and complemented the others for drug hit and drug combination selection. Our results provide evidence that in vivo zPDX drug screening is a promising add-on to current functional drug screening in precision medicine platforms.
Insights
Pediatric relapsed tumors have poor survival rates. This study shows that zebrafish PDX models complement other functional drug screening methods, offering a promising addition to personalized cancer medicine.
Area of Science:
- Pediatric Oncology
- Cancer Genomics
- Drug Discovery
Background:
- Childhood relapsed tumors exhibit poor survival due to heterogeneity and drug resistance.
- Current precision oncology, like the INFORM study, shows molecular profiling benefits only a subset of patients.
- Functional drug testing is needed to complement molecular profiling in pediatric precision oncology.
Purpose of the Study:
- To compare drug screening results from patient-derived spheroid cultures, mouse PDX, organoid-like cultures, and zebrafish PDX (zPDX) models.
- To evaluate the utility of different patient-derived models for selecting anti-cancer drugs and combinations.
- To assess the potential of in vivo zPDX drug screening as part of precision medicine platforms.
Main Methods:
- Utilized molecularly characterized tumor samples from the INFORM study.
- Established and compared four patient-derived models: spheroid cultures, mouse PDX, organoid-like cultures, and zPDX.
- Performed functional drug screening assays on all established models.
Main Results:
- Each tested model (spheroids, mouse PDX, organoids, zPDX) demonstrated unique advantages.
- The models complemented each other in identifying effective drug hits and combinations.
- In vivo zebrafish PDX drug screening showed promise as an add-on to existing functional screening methods.
Conclusions:
- Patient-derived spheroid cultures, mouse PDX, organoids, and zPDX models each offer distinct benefits for drug screening.
- Combining data from multiple functional assays enhances drug hit and combination selection for pediatric precision oncology.
- In vivo zebrafish PDX models represent a valuable and promising tool for enhancing personalized cancer therapy in children.
