Author: Liliana Berube, Randall J Kimple, Kwangok P Nickel, Hannah Sondreal 👨🔬
Affiliation: UW Madison 🌍
Purpose: The fidelity of patient-derived xenografts (PDXs) is crucial for their application in translational research, as it ensures that these models accurately retain the properties of the original patient tumors. While studies in other cancers have shown significant clonal dynamics, genetic alterations, and other changes due to serial passaging, these effects have not been thoroughly investigated in head and neck cancer. Additionally, the impact of these changes on radiation response and other therapeutic outcomes remains unexplored in head and neck cancer.
Methods: Surgical samples of head and neck squamous cell carcinoma were engrafted into the flanks of immunocompromised mice. Radiation response was evaluated at early (< passage 5) and late (> passage 5) stages of passaging by measuring tumor volume with electronic calipers following radiation therapy (2 Gy/day for 5 days/week). Degree of angiogenic activity was evaluated by calculating tissue microvessel density, a ratio of the area of blood vessels to area of tissue.
Results: Radiation therapy reduced tumor volume in both early (<5) and late (>5) stage passaging models. No significant difference in tumor volume reduction in response to radiation was observed between early and late stage passages. Additionally, no significant difference in microvessel density was found between passages.
Conclusion: This work indicates that serial passaging does not significantly alter the radiation response and angiogenic activity of head and neck cancer PDX models. These findings validate the use of late passage PDX models in translational research including future studies on radiation and antiangiogenic therapies. Further validation through single-cell RNA sequencing (scRNAseq), photoacoustic imaging of perfusion, and immunohistochemical staining of proangiogenic proteins will enhance confidence in the fidelity of late passage models and their contribution to translational research.