Preclinical models that accurately predict clinical outcomes are vital for advancing cancer therapeutics. Patient-Derived Xenograft (PDX) models—created by implanting human tumor fragments into immunodeficient mice—maintain the architecture, stromal elements, and molecular heterogeneity of the original tumor. They’re essential for testing new drugs, understanding resistance, and discovering predictive biomarkers.
What Are PDX Models?
In a PDX workflow, fresh tumor samples from patients are engrafted directly into immunodeficient mice. This preserves:
- Three-dimensional tumor architecture
- Human stromal and extracellular matrix components
- Genomic heterogeneity, including mutations, copy-number changes, and gene-expression patterns
For example, our breast cancer PDX models have enabled detailed evaluation of targeted therapies in hormone-receptor and HER2-driven tumors.
Advantages Over Cell-Line and GEM Models
Traditional cell lines have been invaluable, but they often lack the complexity of patient tumors. Genetically engineered mouse (GEM) models capture specific oncogenic events yet miss the full mutational landscape and human microenvironment.
In contrast, PDX models:
- Originate from treatment-experienced patients carrying real-world resistance mechanisms
- Recapitulate human tumor biology more faithfully across serial passages
- Enable “mouse clinical trials” to stratify responders and non-responders
Integrating PDX in Immuno-Oncology
Standard PDX models lack immune components because they use immunodeficient hosts. To evaluate immunotherapies, researchers generate “humanized” PDX mice by co-engrafting human hematopoietic stem cells. This approach:
- Reconstitutes T cells, B cells, and key myeloid populations
- Allows testing of checkpoint inhibitors and cell-based therapies
Despite its promise, humanized PDX still faces challenges like incomplete cytokine networks and potential non-physiological interactions between human immune cells and mouse stroma.
Conclusion
PDX models have become indispensable tools in oncology drug development. They bridge the gap between cell lines and clinical trials by offering a patient-centric platform for efficacy testing, resistance mechanism studies, and biomarker discovery. While no model is perfect, continued refinement of PDX methods will further enhance translational success.