Related Experiment Video
Updated: May 9, 2026
Establishment and Characterization of Patient-Derived Xenograft Models of Anaplastic Thyroid Carcinoma and Head and Neck Squamous Cell Carcinoma
Published on: June 2, 2023
Pretherapeutic drug evaluation by tumor xenografting in anaplastic thyroid cancer
Annette Wunderlich1, Maryna Khoruzhyk, Silvia Roth
1Department of Surgery, Philipps-University Marburg, Marburg, Germany.
Background:
Despite various attempts at modifying usual treatment modalities, anaplastic thyroid cancer (ATC) is still associated with unfavorable prognosis. Results of preclinical investigations are often of limited transferability to clinical tumor biology. Individualized multimodal treatment regimens, including novel growth-inhibiting drugs, might be a future option.
Methods:
Tumor tissue, freshly prepared from a patient operated for ATC, was xenotransplanted to nude mice. While the patient obtained a hyperfractionated external beam radiation, mice carrying xenotransplanted tumors were randomized (n = 6) and treated by multikinase inhibitors (sorafenib [S]: vascular endothelial growth factor receptor [VEGF-R], platelet derived growth factor receptor, RET; vandetanib [V]: VEGF-R, endothelial growth factor receptor [EGF-R]; and MLN8054 [M]: Aurora kinases [AK]). Antiproliferative, antiangiogenic, and proapoptotic effects were evaluated.
Results:
Treatment of successfully xenotransplanted fresh ATC tumor tissue by multikinase inhibitors and aurora kinase inhibitor reduced the tumor volume up to 61% depending on the drug and time of application (3 wk of treatment: 46% [M], 34% [V], 30% [S]; 5 wk of treatment: 61% [S]). Tumor cell proliferation (BrdU) was reduced between 34% and 58% [S] and [V]. Reduction of tumor vascularity was between 67% [V] and 33% [S] and was accompanied by decreased EGF-R/VEGF-R2 receptor activity [V/V,S]. Tumor cell apoptosis (caspase 3 activity) increased up to 2.4-fold [S].
Conclusions:
Successful in vivo evaluation of novel drugs in xenotransplanted fresh tumor tissue allows in-time (while patient receives standard treatment) prospective analysis for possible additional clinical application. However, technical specifications have to be taken into account to obtain stable in vivo tumor growth. Based on the individual results, a tailored clinical drug application seems possible.
Insights
Anaplastic thyroid cancer (ATC) xenografts in mice showed reduced tumor volume and proliferation with novel kinase inhibitors. This preclinical model supports personalized drug selection for improved patient outcomes.
Area of Science:
- Oncology
- Pharmacology
- Translational Medicine
Background:
- Anaplastic thyroid cancer (ATC) has a poor prognosis despite treatment modifications.
- Preclinical study findings often lack clinical relevance.
- Individualized multimodal therapies with novel drugs are a potential future direction.
Observation:
- ATC tumor tissue was xenotransplanted into nude mice.
- Mice with xenografts received multikinase inhibitors (sorafenib, vandetanib) or an aurora kinase inhibitor (MLN8054).
- The patient received hyperfractionated external beam radiation concurrently.
Findings:
- Inhibitors reduced tumor volume by up to 61% in xenografts.
- Tumor cell proliferation decreased by 34-58% with sorafenib and vandetanib.
- Tumor vascularity reduced by 33-67%, with decreased EGF-R/VEGF-R2 activity, and apoptosis increased up to 2.4-fold with sorafenib.
Implications:
- In vivo evaluation of novel drugs in xenografts enables timely analysis for clinical application.
- This approach supports tailored drug selection for individual ATC patients.
- Technical considerations are crucial for stable in vivo tumor growth.
