Patient-Derived Xenografts for Prognostication and Personalized Treatment for Head and Neck Squamous Cell Carcinoma
Open accessAbstract
Overall survival remains very poor for patients diagnosed as having head and neck squamous cell carcinoma (HNSCC). Identification of additional biomarkers and novel therapeutic strategies are important for improving patient outcomes. Patient-derived xenografts (PDXs), generated by implanting fresh tumor tissue directly from patients into immunodeficient mice, recapitulate many of the features of their corresponding clinical cancers, including histopathological and molecular profiles. Using a large collection of PDX models of HNSCC, we demonstrate that rapid engraftment into immunocompromised mice is highly prognostic and show that genomic deregulation of the G1/S checkpoint pathway correlates with engraftment. Furthermore, CCND1 and CDKN2A genomic alterations are predictive of response to the CDK4and CDK6 inhibitor abemaciclib. Overall, our study supports the pursuit of CDK4 and CDK6 inhibitors as a therapeutic strategy for a substantial proportion of HNSCC patients and demonstrates the potential of using PDX models to identify targeted therapies that will benefit patients who have the poorest outcomes.
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PDX models recapitulate the biological property and molecular heterogeneity of human cancers and are an ideal preclinical model for inferring clinical performance.
“PDX models that recapitulate the biological property and molecular heterogeneity of human cancers have been considered as an ideal preclinical model for inferring clinical performance (6, 43)”
From Small-molecule PROTAC mediates targeted protein degradation to treat STAT3-dependent epithelial cancer (2022) · cites this paper as [6]
The Discussion (page not provided) reports that PDX drug responses can mimic clinical-trial responses, supporting their use in preclinical evaluation. It also says this study did not compare matched patient tumors and PDXs at the molecular level and notes limitations including mouse-specific tumor evolution. It therefore does not establish that PDXs generally preserve the molecular heterogeneity of human cancers or are an ideal model for predicting clinical performance. (LLM, conf=0.86)
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Self-citation
- Authors
- Karamboulas, C., Bruce, J. P., Hope, A. J., Meens, J., Huang, S. H., Erdmann, N., Hyatt, E., Pereira, K., Goldstein, D. P., Weinreb, I., Su, J., O’Sullivan, B., Tiedemann, R., Liu, F.-F., Pugh, T. J., Bratman, S. V., Xu, W., & Ailles, L.
- Affiliations
- University Health Network (CA)
- University of Toronto (CA)
- Hospital for Sick Children (CA)
- Corresponding author
- Ailles, Laurie
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 25
- Issue
- 5
- Pages
- 1318-1331.e4
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2899066274
- Cited by
- 94
- References
- 47
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 9 · 2023: 11 · 2022: 16 · 2021: 15 · 2020: 18 · 2019: 6
- FWCI
- 8.66
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research (MOP126203)
- Ontario Institute for Cancer Research
- Princess Margaret Cancer Foundation
- Joe and Cara Finley Centre for Head and Neck Cancer Translational Research
- Wharton Family
- Gordon Tozer
- Topics
- Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- head and neck squamous cell carcinoma, patient-derived xenografts, tumor engraftment, prognostic factors, G1/S checkpoint, CDK4/6 inhibitors, abemaciclib, CCND1, CDKN2A, personalized treatment, immunodeficient mice
- MeSH terms
- Squamous Cell Carcinoma of Head and Neck, Aminopyridines, Animals, Base Sequence, Benzimidazoles, Female, Humans, Male, Middle Aged, Mutation, Neoplasm Recurrence, Local, Prognosis, Regression Analysis, Risk Factors, Multivariate Analysis, Survival Analysis, Mice, SCID, Mice, Inbred NOD, Treatment Outcome, Cyclin D1, Cyclin-Dependent Kinase Inhibitor p16, Xenograft Model Antitumor Assays, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6, Precision Medicine
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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