Targeting Ataxia Telangiectasia-Mutated and Rad3-Related for Anaplastic Thyroid Cancer

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.