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Updated: Nov 2, 2025
An Orthotopic Mouse Model of Anaplastic Thyroid Carcinoma
Published on: April 17, 2013
A High-throughput Approach to Identify Effective Systemic Agents for the Treatment of Anaplastic Thyroid Carcinoma
Ying C Henderson1, Abdallah S R Mohamed1,2,3, Anastasios Maniakas1,4
1Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Background:
Despite the use of aggressive multimodality treatment, most anaplastic thyroid carcinoma (ATC) patients die within a year of diagnosis. Although the combination of BRAF and MEK inhibitors has recently been approved for use in BRAF-mutated ATC, they remain effective in a minority of patients who are likely to develop drug resistance. There remains a critical clinical need for effective systemic agents for ATC with a reasonable toxicity profile to allow for rapid translational development.
Material And Methods:
Twelve human thyroid cancer cell lines with comprehensive genomic characterization were used in a high-throughput screening (HTS) of 257 compounds to select agents with maximal growth inhibition. Cell proliferation, colony formation, orthotopic thyroid models, and patient-derived xenograft (PDX) models were used to validate the selected agents.
Results:
Seventeen compounds were effective, and docetaxel, LBH-589, and pralatrexate were selected for additional in vitro and in vivo analysis as they have been previously approved by the US Food and Drug Administration for other cancers. Significant tumor growth inhibition (TGI) was detected in all tested models treated with LBH-589; pralatrexate demonstrated significant TGI in the orthotopic papillary thyroid carcinoma model and 2 PDX models; and docetaxel demonstrated significant TGI only in the context of mutant TP53.
Conclusions:
HTS identified classes of systemic agents that demonstrate preferential effectiveness against aggressive thyroid cancers, particularly those with mutant TP53. Preclinical validation in both orthotopic and PDX models, which are accurate in vivo models mimicking tumor microenvironment, may support initiation of early-phase clinical trials in non-BRAF mutated or refractory to BRAF/MEK inhibition ATC.
Insights
New drug screening identified effective systemic agents for aggressive thyroid cancer, offering hope for patients resistant to current treatments. These findings support clinical trials for anaplastic thyroid carcinoma (ATC) and other aggressive thyroid cancers.
Area of Science:
- Oncology
- Drug Discovery
- Genomics
Background:
- Anaplastic thyroid carcinoma (ATC) has a poor prognosis despite aggressive treatment.
- Current therapies like BRAF/MEK inhibitors benefit only a subset of patients and drug resistance is common.
- There is a critical need for novel, well-tolerated systemic agents for ATC.
Purpose of the Study:
- To identify novel systemic agents with maximal growth inhibitory effects against aggressive thyroid cancers.
- To validate the efficacy of selected compounds in preclinical in vitro and in vivo models.
- To explore potential therapeutic strategies for BRAF-mutated and non-BRAF-mutated ATC.
Main Methods:
- High-throughput screening (HTS) of 257 compounds against 12 genomically characterized human thyroid cancer cell lines.
- Validation of selected agents using cell proliferation assays, colony formation assays, orthotopic thyroid cancer models, and patient-derived xenograft (PDX) models.
- In vitro and in vivo analysis of FDA-approved drugs including docetaxel, LBH-589, and pralatrexate.
Main Results:
- Seventeen compounds demonstrated efficacy in HTS.
- LBH-589 showed significant tumor growth inhibition (TGI) across all tested models.
- Pralatrexate demonstrated significant TGI in an orthotopic papillary thyroid carcinoma model and two PDX models.
- Docetaxel showed significant TGI specifically in the context of mutant TP53.
Conclusions:
- HTS identified systemic agents effective against aggressive thyroid cancers, particularly those with mutant TP53.
- Preclinical validation in orthotopic and PDX models supports the initiation of early-phase clinical trials.
- These findings offer potential new treatment avenues for patients with non-BRAF mutated or BRAF/MEK inhibitor-refractory ATC.
