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Updated: Nov 11, 2025
Establishment and Characterization of Patient-Derived Xenograft Models of Anaplastic Thyroid Carcinoma and Head and Neck Squamous Cell Carcinoma
Published on: June 2, 2023
Efficacy of adavosertib therapy against anaplastic thyroid cancer
Yu-Ling Lu1,2,3, Yu-Tung Huang4, Ming-Hsien Wu1,2,3
1Department of Internal Medicine, New Taipei Municipal TuCheng Hospital, New Taipei City, Taiwan.
Abstract:
Wee1 is a kinase that regulates the G2/M progression by the inhibition of CDK1, which is critical for ensuring DNA damage repair before initiation of mitotic entry. Targeting Wee1 may be a potential strategy in the treatment of anaplastic thyroid cancer, a rare but lethal disease. The therapeutic effects of adavosertib, a Wee1 inhibitor for anaplastic thyroid cancer was evaluated in this study. Adavosertib inhibited cell growth in three anaplastic thyroid cancer cell lines in a dose-dependent manner. Cell cycle analysis revealed cells were accumulated in the G2/M phase. Adavosertib induced caspase-3 activity and led to apoptosis. Adavosertib monotherapy showed significant retardation of the growth of two anaplastic thyroid cancer tumor models. The combination of adavosertib with dabrafenib and trametinib revealed strong synergism in vitro and demonstrated robust suppression of tumor growth in vivo in anaplastic thyroid cancer xenograft models with BRAFV600E mutation. The combination of adavosertib with either sorafenib or lenvatinib also demonstrated synergism in vitro and had strong inhibition of tumor growth in vivo in an anaplastic thyroid cancer xenograft model. No appreciable toxicity appeared in mice treated with either a single agent or combination treatment. Our findings suggest adavosertib holds the promise for the treatment of patients with anaplastic thyroid cancer.
Insights
Adavosertib, a Wee1 inhibitor, shows promise for treating anaplastic thyroid cancer. It effectively inhibits cancer cell growth, induces apoptosis, and suppresses tumor growth, with no significant toxicity observed in preclinical models.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Anaplastic thyroid cancer (ATC) is a rare and aggressive malignancy.
- Wee1 kinase regulates cell cycle progression and DNA damage repair, making it a potential therapeutic target.
- Inhibition of Wee1 kinase may offer a novel strategy for ATC treatment.
Purpose of the Study:
- To evaluate the therapeutic efficacy of adavosertib, a Wee1 inhibitor, in anaplastic thyroid cancer.
- To assess the synergistic effects of adavosertib in combination with other targeted therapies.
- To determine the safety profile of adavosertib in preclinical ATC models.
Main Methods:
- In vitro studies using three ATC cell lines to assess adavosertib's effects on cell growth, cell cycle, and apoptosis.
- In vivo studies using ATC xenograft models to evaluate adavosertib monotherapy and combination therapies.
- Combination therapies included adavosertib with dabrafenib/trametinib, sorafenib, or lenvatinib.
Main Results:
- Adavosertib demonstrated dose-dependent inhibition of ATC cell growth and induced G2/M phase arrest.
- Adavosertib treatment led to increased caspase-3 activity and apoptosis.
- Adavosertib monotherapy and combination therapies significantly suppressed tumor growth in vivo with no observed toxicity.
Conclusions:
- Adavosertib exhibits potent anti-cancer activity against anaplastic thyroid cancer.
- Combination therapies with adavosertib show significant synergistic effects and robust tumor suppression.
- Adavosertib is a promising therapeutic agent for anaplastic thyroid cancer treatment.
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