Zebrafish xenograft models as a fast platform for metastasis diagnosis and cisplatin response of head and neck squamous cell carcinoma
4 affiliations
- 1Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People's Hospital (Affiliated People's Hospital) Hangzhou Medical College Hangzhou Zhejiang China
- 2Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital) Hangzhou Medical College Hangzhou Zhejiang China
- 3Department of Head and Neck Surgery Zhejiang Cancer Hospital Hangzhou China
- 4Department of Radiology Zhejiang Provincial People's Hospital Hangzhou China
Abstract
Background: Head and neck squamous cell carcinoma (HNSCC) is characterized by clinically undetectable early metastasis and a poor prognosis at locally advanced and recurrent metastatic stages. Platinum‐based resistance remains a major limitation to treatment efficacy. Currently, no reliable biomarkers are available to identify lymph node metastasis or to predict therapeutic sensitivity. Therefore, this study aimed to develop a predictive model to address these clinical challenges.
Methods: Four cell lines (CAL‐27, FaDu, Leuk1, NOEC) were employed to establish zebrafish cell‐derived xenograft (zCDX) models and assess the differential metastatic potential. Surgical or biopsy samples from, respectively, 20 and 14 HNSCC patients were used for building and validating the zebrafish patient‐derived xenograft (zPDX) models. Cisplatin‐sensitive HNSCC cell lines (CAL‐27 and FaDu) and their cisplatin‐resistant sublines (CAL‐27‐DDP and FaDu‐DDP) were established, and the differential responses to cisplatin were evaluated in both murine and zCDX models. Additionally, to assess the patient‐specific therapeutic efficacy of cisplatin, zPDX models were generated from four patient‐derived surgical specimens and a supplementary biopsy for preliminary validation.
Results: The zebrafish xenograft model recapitulated the invasive phenotype of the HNSCC cell lines. The model distinguished between metastatic and non‐metastatic disease with high accuracy (AUC = 0.98). It faithfully reproduced the cisplatin sensitivity and resistance patterns identified in corresponding in vitro and murine models. Moreover, it showed strong concordance with patient‐specific cisplatin responses.
Conclusions: The zPDX model provides a rapid, efficient, clinically applicable platform for predicting metastasis and evaluating platinum‐based therapy responses in HNSCC, facilitating the design of scientifically grounded personalized treatment.
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BibTeX
@article{chen2026zebrafish,
title = {{Zebrafish xenograft models as a fast platform for metastasis diagnosis and cisplatin response of head and neck squamous cell carcinoma}},
author = {Lu Chen and Shu Sun and Yujia Liu and Liehao Jiang and Cuiyun Wu and Ting Liu and Yujiao Zhao and Yuwei Liu and Lu Liu and Qi Wang and Xiaowei Zheng and Ping Huang},
journal = {Animal Models and Experimental Medicine},
year = {2026},
month = aug,
doi = {10.1002/ame2.70282},
url = {https://doi.org/10.1002/ame2.70282},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Zebrafish xenograft models as a fast platform for metastasis diagnosis and cisplatin response of head and neck squamous cell carcinoma
AU - Lu Chen
AU - Shu Sun
AU - Yujia Liu
AU - Liehao Jiang
AU - Cuiyun Wu
AU - Ting Liu
AU - Yujiao Zhao
AU - Yuwei Liu
AU - Lu Liu
AU - Qi Wang
AU - Xiaowei Zheng
AU - Ping Huang
PY - 2026
DA - 2026/08/20
JO - Animal Models and Experimental Medicine
DO - 10.1002/ame2.70282
UR - https://doi.org/10.1002/ame2.70282
AB - Background: Head and neck squamous cell carcinoma (HNSCC) is characterized by clinically undetectable early metastasis and a poor prognosis at locally advanced and recurrent metastatic stages. Platinum‐based resistance remains a major limitation to treatment efficacy. Currently, no reliable biomarkers are available to identify lymph node metastasis or to predict therapeutic sensitivity. Therefore, this study aimed to develop a predictive model to address these clinical challenges. Methods: Four cell lines (CAL‐27, FaDu, Leuk1, NOEC) were employed to establish zebrafish cell‐derived xenograft (zCDX) models and assess the differential metastatic potential. Surgical or biopsy samples from, respectively, 20 and 14 HNSCC patients were used for building and validating the zebrafish patient‐derived xenograft (zPDX) models. Cisplatin‐sensitive HNSCC cell lines (CAL‐27 and FaDu) and their cisplatin‐resistant sublines (CAL‐27‐DDP and FaDu‐DDP) were established, and the differential responses to cisplatin were evaluated in both murine and zCDX models. Additionally, to assess the patient‐specific therapeutic efficacy of cisplatin, zPDX models were generated from four patient‐derived surgical specimens and a supplementary biopsy for preliminary validation. Results: The zebrafish xenograft model recapitulated the invasive phenotype of the HNSCC cell lines. The model distinguished between metastatic and non‐metastatic disease with high accuracy (AUC = 0.98). It faithfully reproduced the cisplatin sensitivity and resistance patterns identified in corresponding in vitro and murine models. Moreover, it showed strong concordance with patient‐specific cisplatin responses. Conclusions: The zPDX model provides a rapid, efficient, clinically applicable platform for predicting metastasis and evaluating platinum‐based therapy responses in HNSCC, facilitating the design of scientifically grounded personalized treatment.
SN - 2096-5451
SN - 2576-2095
ER -