ArticleRadiation oncology (London, England)2017
Overcoming hypoxia-induced tumor radioresistance in non-small cell lung cancer by targeting DNA-dependent protein kinase in combination with carbon ion irradiation.
Article in Radiation oncology (London, England), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 106 citations in OpenAlex.
- NOP58 modulates radiosensitivity in non-small cell lung cancer via DDX18-mediated DNA damage repair.Journal of radiation research · 2026Article
- Review
- Effect of Reoxygenation on Radioresistance of Chronically Hypoxic A549 Non-Small Cell Lung Cancer (NSCLC) Cells Following X-Ray and Carbon Ion Exposure.International journal of molecular sciences · 2025Article
- Carbon-Ion Radiotherapy for Hepatocellular Carcinoma: Current Status and Future Prospects: A Narrative Review.Journal of clinical medicine · 2025Review
- Characterizing diamond detectors for various dose and dose rate measurements in scanned carbon and oxygen beams.Medical physics · 2025Article
- Targeting DNA Damage Response-Mediated Resistance in Non-Small Cell Lung Cancer: From Mechanistic Insights to Drug Development.Current oncology (Toronto, Ont.) · 2025Review
- Tumour hypoxia in driving genomic instability and tumour evolution.Nature reviews. Cancer · 2025Review
- HPV and p53 Status as Precision Determinants of Head and Neck Cancer Response to DNA-PKcs Inhibition in Combination with Irradiation.Molecular cancer therapeutics · 2025Article
- Oxygen consumption measurements at ultra-high dose rate over a wide LET range.Medical physics · 2025Article
- Bone matching versus tumor matching in image-guided carbon ion radiotherapy for locally advanced non-small cell lung cancer.Radiation oncology (London, England) · 2024Article
- First Dosimetric and Biological Verification for Spot-Scanning Hadron Arc Radiation Therapy With Carbon Ions.Advances in radiation oncology · 2024Article
- Value of Carbon-Ion Radiation Therapy for Breast Cancer.International journal of particle therapy · 2024Review
- Potential Benefits of Combining Proton or Carbon Ion Therapy with DNA Damage Repair Inhibitors.Cells · 2024Review
- Feedback loop between hypoxia and energy metabolic reprogramming aggravates the radioresistance of cancer cells.Experimental hematology & oncology · 2024Review
- Hypoxia predicts favorable response to carbon ion radiotherapy in non-small cell lung cancer (NSCLC) defined byQuantitative imaging in medicine and surgery · 2024Article
- NF-κB in the Radiation Response of A549 Non-Small Cell Lung Cancer Cells to X-rays and Carbon Ions under Hypoxia.International journal of molecular sciences · 2024Article
- Hypoxia Modulates Radiosensitivity and Response to Different Radiation Qualities in A549 Non-Small Cell Lung Cancer (NSCLC) Cells.International journal of molecular sciences · 2024Article
- Establishment and Application of Novel Hypoxia-driven Dual-reporter Model to Investigate Hypoxic Impact on Radiation Sensitivity in Human Nasopharyngeal Carcinoma Xenografts.Journal of Cancer · 2024Article
- Targeting the DNA Damage Response for Cancer Therapy.International journal of molecular sciences · 2023Review
- Non-small cell lung cancers (NSCLCs) oncolysis using coxsackievirus B5 and synergistic DNA-damage response inhibitors.Signal transduction and targeted therapy · 2023Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundHypoxia-induced radioresistance constitutes a major obstacle for a curative treatment of cancer. The aim of this study was to investigate effects of photon and carbon ion irradiation in combination with inhibitors of DNA-Damage Response (DDR) on tumor cell radiosensitivity under hypoxic conditions.
methodsHuman non-small cell lung cancer (NSCLC) models, A549 and H1437, were irradiated with dose series of photon and carbon ions under hypoxia (1% O
resultsThe OER at 30% survival for photon irradiation of A549 cells was 1.4. The maximal oxygen effect measured as survival ratio was 2.34 at 8 Gy photon irradiation of A549 cells. In contrast, no significant oxygen effect was found after carbon ion irradiation. Accordingly, the relative effect of 6 Gy carbon ions was determined as 3.8 under normoxia and. 4.11 under hypoxia. ATM and DNA-PK inhibitors dose dependently sensitized tumor cells for both radiation qualities. For 100 nM DNAPKi the survival ratio at 4 Gy more than doubled from 1.59 under normoxia to 3.3 under hypoxia revealing a strong radiosensitizing effect under hypoxic conditions. In contrast, this ratio only moderately increased after photon irradiation and ATMi under hypoxia. The most effective treatment was combined carbon ion irradiation and DNA damage repair inhibition.
conclusionsCarbon ions efficiently eradicate hypoxic tumor cells. Both, ATMi and DNAPKi elicit radiosensitizing effects. DNAPKi preferentially sensitizes hypoxic cells to radiotherapy.
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