From bench to bedside: Advancements in patient-derived xenografts for predicting therapy outcomes in colorectal cancer

Table 1 Comparison of zebrafish embryo and murine patient-derived xenograft models in colorectal cancer

Category	Zebrafish PDX	Mouse PDX
Host	Embryos are usually used (immune system not fully developed); multiple transgenic zebrafish lines available	Immunodeficient mice are required for xenografting (e.g., non-obese diabetic-severe combined immunodeficient-γ, nude)
Physiological alignment	70% synteny to humans - representing 82% of genes associated with human diseases; pharmacokinetics differ from mammals	90% synteny to humans; more predictive drug bioavailability and clearance
Engraftment site	Perivitelline space or yolk sac	Subcutaneous or orthotopic
Tumor material	1 mm to 3 mm fragment or cell suspension; no expansion needed for chemoprofile experiments; compatible with biopsies	3 mm to 5 mm fragment or dissociated cells; often needs expanded in culture
Tumor microenvironment and stroma fidelity	Can temporarily retain native tumor architecture and early immune interactions; models early metastatic steps	Maintains three-dimensional architecture and tumor heterogeneity in early passages but over time, human stroma replaced by mouse stroma
Temperature	28-37 °C (usually intermediate temperatures for both the graft and the fish to thrive are required)	37 °C
Time to results (chemoprofiling)	Days to weeks	Weeks to months; impractical for time sensitive clinical decisions
Sample throughput	High	Low
Xenograft monitoring and imaging	Variables usually monitored in studies - changes in tumor size, apoptosis, micro metastasis; stereo or confocal microscopy; compatible with automation for injection/imaging	Variables usually monitored in studies - tumor volume, metastasis, survival; calipers, bioluminescence, imaging (e.g., ultrasound, small-animal magnetic resonance imaging/computed tomography), postmortem pathology
Cost	Low	High
Ethical burden	No ethical approval required before 120 hours post fertilizations; better aligns with 3R principles; minimal tissue needed, reducing ethical concerns	Subject to strict animal welfare regulations; ethical constraints limit large-scale use; requires ethical approval and complex logistics (biosafety, permits)

PDX: Patient-derived xenograft.