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Updated: May 28, 2025
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Targeting Ataxia Telangiectasia-Mutated and Rad3-Related for Anaplastic Thyroid Cancer
Shu-Fu Lin1,2, Chuen Hsueh2,3, Wei-Yi Chen4
1Division of Endocrinology and Metabolism, Department of Internal Medicine, New Taipei Municipal TuCheng Hospital, New Taipei City 23652, Taiwan.
Background:
Anaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies and has a poor prognosis. Ataxia telangiectasia mutated and Rad3 related (ATR) is a key regulator for the DNA damage response and a potential target to treat cancer.
Methods:
We assessed the efficacy of BAY 1895344, an ATR inhibitor, in three ATC cell lines.
Results:
BAY 1895344 caused dose-response cytotoxicity in three ATC cell lines. BAY 1895344 induced S-phase and G2-phase arrest, activated caspase-3 activity and induced apoptosis in ATC cells. BAY 1895344 meaningfully retarded the tumor growth of an ATC xenograft model. BAY 1895344 therapy, combined with dabrafenib and trametinib, had synergism in vitro and revealed robust tumor growth suppression in vivo in two xenograft models of ATC harboring mutant BRAFV600E. Furthermore, the combination of BAY 1895344 with lenvatinib was more effective than either agent alone in a xenograft model of ATC.
Conclusions:
These results reveal that BAY 1895344 has potential in treating ATC.
Insights
BAY 1895344, an ATR inhibitor, shows promise in treating anaplastic thyroid cancer (ATC). It effectively reduced cancer cell growth and induced apoptosis, with combination therapies demonstrating significant tumor suppression.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Anaplastic thyroid cancer (ATC) is a highly aggressive malignancy with a poor patient prognosis.
- The Ataxia Telangiectasia Mutated and Rad3 Related (ATR) kinase is crucial for DNA damage response and represents a potential therapeutic target in cancer.
Purpose of the Study:
- To evaluate the efficacy of BAY 1895344, a novel ATR inhibitor, as a potential treatment for anaplastic thyroid cancer.
Main Methods:
- Assessed the in vitro cytotoxicity of BAY 1895344 across three ATC cell lines.
- Investigated the effects of BAY 1895344 on cell cycle progression, apoptosis, and tumor growth in ATC xenograft models.
- Evaluated the synergistic effects of BAY 1895344 in combination with targeted therapies (dabrafenib, trametinib, lenvatinib).
Main Results:
- BAY 1895344 demonstrated dose-dependent cytotoxicity and induced apoptosis in ATC cell lines.
- The ATR inhibitor significantly inhibited tumor growth in vivo and showed synergistic effects when combined with BRAF/MEK inhibitors in BRAF-mutant ATC models.
- Combination therapy with BAY 1895344 and lenvatinib exhibited enhanced efficacy compared to monotherapy in an ATC xenograft model.
Conclusions:
- BAY 1895344 exhibits significant anti-cancer activity against anaplastic thyroid cancer.
- The findings support the potential of BAY 1895344 as a therapeutic agent for ATC, particularly in combination strategies.
