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Updated: Aug 9, 2025
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Huayun Yan1, Yingfang Ma1, Xinyue Zhou2
1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center.
Abstract:
Anaplastic thyroid cancer (ATC) is a rare but lethal malignancy with a dismal prognosis. There is an urgent need for more in-depth research on the carcinogenesis and development of ATC, as well as therapeutic methods, since standard treatments are essentially depleted in ATC patients. However, low prevalence has hampered thorough clinical studies and the collection of tissue samples, so little progress has been achieved in creating effective treatments. We used genetic engineering to create a conditionally inducible ATC murine model (mATC) in a C57BL/6 background. The ATC murine model was genotyped by TPO-cre/ERT2; BrafCA/wt; Trp53ex2-10/ex2-10 and induced by intraperitoneal injection with tamoxifen. With the murine model, we investigated the tumor dynamics (tumor size ranged from 12.4 mm2 to 32.5 mm2 after 4 months of induction), survival (the median survival period was 130 days), and metastasis (lung metastases occurred in 91.6% of mice) curves and pathological features (characterized by Cd8, Foxp3, F4/80, Cd206, Ki67, and Caspase-3 immunohistochemical staining). The results indicated that spontaneous mATC possesses highly similar tumor dynamics and immunological microenvironment to human ATC tumors. In conclusion, with high similarity in pathophysiological features and unified genotypes, the mATC model resolved the shortage of clinical ATC tissue and sample heterogeneity to some extent. Therefore, it would facilitate the mechanism and translational studies of ATC and provide an approach to investigate the treatment potential of small molecular drugs and immunotherapy agents for ATC.
Insights
Researchers developed a novel murine model for anaplastic thyroid cancer (ATC). This model mimics human ATC's tumor growth, metastasis, and immune microenvironment, aiding in developing new treatments.
Area of Science:
- Oncology
- Genetics
- Immunology
Background:
- Anaplastic thyroid cancer (ATC) is a rare, aggressive malignancy with limited treatment options.
- Low patient prevalence hinders clinical research and tissue sample collection for ATC studies.
- There is a critical need for effective therapeutic strategies and a better understanding of ATC carcinogenesis.
Purpose of the Study:
- To develop and characterize a genetically engineered, conditionally inducible murine model for anaplastic thyroid cancer (mATC).
- To investigate the tumor dynamics, survival, metastasis, and immunological microenvironment of the mATC model.
- To establish a preclinical platform for studying ATC mechanisms and evaluating potential therapies.
Main Methods:
- Genetic engineering of a C57BL/6 mouse model with TPO-cre/ERT2; BrafCA/wt; Trp53ex2-10/ex2-10 genotype.
- Induction of anaplastic thyroid cancer in the murine model via tamoxifen injection.
- Analysis of tumor size, survival rates, lung metastasis, and immunohistochemical staining (Cd8, Foxp3, F4/80, Cd206, Ki67, Caspase-3).
Main Results:
- The mATC model exhibited significant tumor growth (12.4–32.5 mm² within 4 months) and a median survival of 130 days.
- High incidence of lung metastases (91.6%) was observed in the mATC model.
- Immunohistochemical analysis revealed an immunological microenvironment similar to human ATC.
Conclusions:
- The developed mATC model closely replicates human ATC's pathophysiological features and genotype.
- This model addresses limitations in clinical tissue availability and sample heterogeneity for ATC research.
- The mATC model serves as a valuable platform for mechanistic studies and preclinical evaluation of small molecule drugs and immunotherapies for ATC.
