ArticleJournal of advanced research2025
Targeting ATM enhances radiation sensitivity of colorectal cancer by potentiating radiation-induced cell death and antitumor immunity.
Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Mechanisms and advances of drug resistance in colorectal cancer: A systematic overview of multi-layered regulatory networks.Translational oncology · 2026Review
- PARG inhibition in ATM-deficient prostate cancer: from mechanistic discovery to therapeutic potential.Journal of translational medicine · 2026Article
- C5aR1 and cGAS/STING and their possible involvement in radiosensitivity of colorectal cancer.iScience · 2026Review
- Review
- MUC14 suppresses lung adenocarcinoma via integrin α8β6/PI3K/AKT/MAPK modulating cisplatin response and immunity.Scientific reports · 2026Article
- Association of radiotherapy with atrial fibrillation-related gene expression in breast cancer patients: a study based on the TCGA-BRCA database.Discover oncology · 2026Article
- Glutamine metabolism and its roles in tumor radiotherapy by regulating DNA damage repair.Frontiers in cell and developmental biology · 2026Review
- Targeting the cGAS-STING Pathway in Gastrointestinal Cancers: Modulating Tumor-associated Inflammation for Therapeutic Effect.Current drug targets · 2026Review
- Tumor irradiation induced immunogenic response: the impact of DNA damage induction and misrepair.Radiation oncology (London, England) · 2025Review
- XRCC2 knockdown effectively sensitizes esophageal cancer to albumin-paclitaxel in vitro and in vivo.Biochemical genetics · 2025Article
- Application of Immune Checkpoint Inhibitors in Cancer.MedComm · 2025Review
- In silico and in vitro assessment of TP53, ATM, RAD51, and BAX genes in gastric cancer and their contribution to radiotherapy resistance.Hereditas · 2025Article
- Long Non-Coding RNA LOC401312 Induces Radiosensitivity Through Upregulation of CPS1 in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2025Article
- Targeting DNA Damage Repair to Enhance Antitumor Immunity in Radiotherapy: Mechanisms and Opportunities.International journal of molecular sciences · 2025Review
- AI-driven immunotherapy: synergizing with radiotherapy to reconfigure the tumor microenvironment and treatment landscape.Frontiers in pharmacology · 2025Review
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThe efficacy of radiotherapy in colorectal cancer (CRC) is often limited by radiation resistance. Ataxia telangiectasia mutated (ATM) is well known for its role in repairing double-strand DNA breaks within the DNA damage response (DDR) pathway. However, whether ATM mediates other mechanisms contributing to radiation resistance remains insufficiently investigated.
objectivesThis study investigates how targeting ATM enhances CRC radiation sensitivity and evaluates combination strategies to improve radiotherapy outcomes.
methodsClinical specimens were analyzed to correlate ATM activation with radiotherapy response. Functional assays, including EdU, cell viability, clonogenic survival, and apoptosis assays, were used to assess the impact of ATM inhibition on radiation sensitivity. Mechanistic insights were gained through RNA-seq, RT-qPCR, western blotting, ELISA, immunofluorescence, flow cytometry, ChIP-qPCR, and co-immunoprecipitation. In vivo efficacy was evaluated using subcutaneous tumor models in nude, BALB/c, and C57BL/6J mice.
resultsHigh ATM phosphorylation levels correlated with poor radiotherapy response in CRC patients. ATM inhibition enhanced radiation sensitivity in both in vitro and in vivo models. Mechanistically, ATM inhibition increased radiation-induced ROS accumulation and mitochondrial damage, leading to the release of mitochondrial DNA (mtDNA) into the cytosol and activation of the STING-type I interferon pathway. This enhanced CD8+ T cell infiltration and boosted antitumor immunity. Additionally, ATM inhibition partially alleviated the radiation-induced upregulation of PD-L1, likely through the ATM/NEMO/NF-κB pathway. Notably, triple therapy combining radiotherapy, an ATM inhibitor, and anti-PD-L1 achieved superior tumor control and remission in mouse models, including large, treatment-resistant tumors.
conclusionTargeting ATM enhances radiation-induced tumor cell death and boosts antitumor immune responses, offering a promising strategy to overcome CRC radiation resistance. The synergy of radiotherapy, ATM inhibitior, and immune checkpoint blockade highlights a novel therapeutic approach for CRC management.
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