Targeting ataxia telangiectasia-mutated and Rad3-related for anaplastic thyroid cancer Journal Article
| Authors: | Lin, S. F.; Hsueh, C.; Chen, W. Y.; Chou, T. C.; Wong, R. J. |
| Article Title: | Targeting ataxia telangiectasia-mutated and Rad3-related for anaplastic thyroid cancer |
| Abstract: | 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. © 2025 by the authors. |
| Keywords: | immunohistochemistry; controlled study; human cell; overall survival; cancer growth; monotherapy; nonhuman; flow cytometry; cell proliferation; mouse; animal tissue; cell viability; dna damage; cell survival; progression free survival; apoptosis; gene expression; confocal microscopy; animal experiment; animal model; caspase 3; antineoplastic activity; cytotoxicity; tumor xenograft; cancer inhibition; western blotting; cell cycle arrest; tumor growth; combination therapy; centrifugation; atr; immunofluorescence microscopy; growth inhibition; ataxia telangiectasia; checkpoint kinase rad3; kinase inhibitor; anaplastic thyroid cancer; anaplastic thyroid carcinoma; spectrophotometry; dabrafenib; trametinib; lenvatinib; human; female; article; methylcellulose; bay 1895344; elimusertib; dextro lactate dehydrogenase; 8305c cell line; thyroid anaplastic carcinoma cell line |
| Journal Title: | Cancers |
| Volume: | 17 |
| Issue: | 3 |
| ISSN: | 2072-6694 |
| Publisher: | MDPI |
| Date Published: | 2025-02-01 |
| Start Page: | 359 |
| Language: | English |
| DOI: | 10.3390/cancers17030359 |
| PROVIDER: | scopus |
| PMCID: | PMC11816221 |
| PUBMED: | 39941729 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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