Patient-Derived Zebrafish Larvae Xenografts for Drug Efficacy and Stroma-Interaction Studies

Our laboratory offers a specialized patient-derived zebrafish larvae xenograft (PDZX) platform as a human-relevant New Approach Methodology (NAM) for rapid, real-time efficacy and toxicity profiling. Utilizing larval stages <5 days post-fertilization, we provide a pragmatic, 3R-compliant route to bridge in vitro data and mammalian studies. By using transgenic strains, we supplement traditional drug sensitivity assays with high-resolution imaging of the tumor and its interaction with the host immune, endothelial, and nervous systems.

While our platforms are adaptable to diverse therapeutic areas, including CNS and neuropharmacology, our current work focuses on pancreatic cancer. We utilize a library of characterized patient-derived organoids to determine precise pharmacological metrics, such as IC50 (potency) and AUC (total effect). These human models are directly integrated into our zebrafish xenograft pipeline for in vivo validation, bridging the gap between in vitro sensitivity and real-time drug response while accounting for complex host-system interactions.

We seek to join Horizon Europe consortia to contribute to WPs focused on drug sensitivity assays and the delivery of robust pharmacology/toxicology evidence packages for new chemical entities and novel molecular modalities. Our platform offers specific mechanistic readouts related to tumor-stroma interaction, strengthening translational confidence through a validated 3R-compliant model.