ArticleCell & bioscience2022
PTEN mutant non-small cell lung cancer require ATM to suppress pro-apoptotic signalling and evade radiotherapy.
Article in Cell & bioscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- AAV9-MediatedPharmaceutics · 2026Article
- Targeting ubiquitin signaling vulnerabilities in KEAP1-inactivated lung cancer.The EMBO journal · 2026Article
- The cross-talk between GSK-3β, RKIP, and PTEN as potential targets for therapeutic implications in cancer: a comprehensive insight.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2026Review
- Mechanisms Underlying Radioresistance and Reversal Strategies in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2025Review
- HIV Integration into the PTEN Gene and Its Tumor Microenvironment Implications for Lung Cancer.Current oncology (Toronto, Ont.) · 2025Article
- The oncogenic axis YAP/MYC/EZH2 impairs PTEN tumor suppression activity enhancing lung tumorigenicity.Cell death discovery · 2024Article
- Pten knockout affects drug resistance differently in melanoma and kidney cancer.Pharmacological reports : PR · 2023Article
- Review
- Therapeutic Implications of PTEN in Non-Small Cell Lung Cancer.Pharmaceutics · 2023Review
- Cancer resistance via the downregulation of the tumor suppressorsExploration of targeted anti-tumor therapy · 2023Review
- BPR0C261, An Analogous of Microtubule Disrupting Agent D-24851 Enhances the Radiosensitivity of Human Non-Small Cell Lung Cancer Cells via p53-Dependent and p53-Independent Pathways.International journal of molecular sciences · 2022Article
- Article
- The Role of PTEN in Epithelial-Mesenchymal Transition.Cancers · 2022Review
- A Review: Genetic Mutations as a Key to Unlocking Drug Resistance in Cervical Cancer.Cancer control : journal of the Moffitt Cancer CenterReview
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundDespite advances in treatment of patients with non-small cell lung cancer, carriers of certain genetic alterations are prone to failure. One such factor frequently mutated, is the tumor suppressor PTEN. These tumors are supposed to be more resistant to radiation, chemo- and immunotherapy.
resultsWe demonstrate that loss of PTEN led to altered expression of transcriptional programs which directly regulate therapy resistance, resulting in establishment of radiation resistance. While PTEN-deficient tumor cells were not dependent on DNA-PK for IR resistance nor activated ATR during IR, they showed a significant dependence for the DNA damage kinase ATM. Pharmacologic inhibition of ATM, via KU-60019 and AZD1390 at non-toxic doses, restored and even synergized with IR in PTEN-deficient human and murine NSCLC cells as well in a multicellular organotypic ex vivo tumor model.
conclusionPTEN tumors are addicted to ATM to detect and repair radiation induced DNA damage. This creates an exploitable bottleneck. At least in cellulo and ex vivo we show that low concentration of ATM inhibitor is able to synergise with IR to treat PTEN-deficient tumors in genetically well-defined IR resistant lung cancer models.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.