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Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
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Artemis (DCLRE1C) Acts as a Target to Enhance Radiotherapy Response in Triple-Negative Breast Cancer
Vasudeva Bhat1,2,3, Kelsie L Thu4,5, Anayra de Fatima Goncalves Santiago1
1Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 3K7, Canada.
Cancers
|October 29, 2025
Summary
Targeting Artemis, a novel radioresistance gene, can enhance radiotherapy response in triple-negative breast cancer (TNBC). Inhibiting Artemis promotes radiosensitization and improves treatment outcomes for TNBC patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Triple-negative breast cancer (TNBC) lacks biomarkers and effective strategies against radioresistance, leading to poor outcomes.
- Identifying novel radioresistance genes is crucial for improving radiotherapy response in TNBC.
Purpose of the Study:
- To identify and characterize novel radioresistance genes in TNBC.
- To evaluate Artemis as a potential therapeutic target to enhance radiotherapy efficacy in TNBC.
Main Methods:
- Genome-wide CRISPR screen in TNBC cells to identify radioresistance genes.
- In vitro and in vivo assays (clonogenic, xenograft) to assess Artemis function and radiosensitization.
- RNA-sequencing and senescence assays to elucidate underlying mechanisms.
Main Results:
- Artemis was identified as a key radioresistance gene in TNBC.
- Artemis knockout sensitized TNBC cells to radiation, reducing proliferation and enhancing RT effects in vitro and in vivo.
- Artemis depletion induced cellular senescence, mediating its radiosensitizing effects.
Conclusions:
- Artemis plays a critical role in TNBC proliferation and radioresistance.
- Artemis is a potential biomarker for radiation sensitivity and a therapeutic target to improve RT efficacy in TNBC.
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