{
  "abstract": "NHEJ is one of the preferred DNA-damage-repairing mechanisms for human cells, due to its rapid onset and activity throughout the cell cycle. It is, nevertheless, error-prone and highly relevant in numerous oncological malignancies. In recent years, it has gained a lot of attention as a target either for cancer treatment or as pharmacological- and radio-sensitization approaches. This study evaluated the genotoxicity and radiosensitization potential of three DNA-PK inhibitors (PIK-75, M3814, and CC-115) in breast cancer by comparing MDA-MB-231 and MCF-7 breast cancer cell lines, selected based on reported differences in DNA-repair characteristics and relative NHEJ dependence. Cells were preincubated with the DNA-PK inhibitors, using four different concentrations either in monotherapy or in combination with a DNA damage inducer (doxorubicin or [64Cu]CuCl2). Viability was measured by MTS assays at 24, 48, and 72 h, while the DNA damage was measured by γH2AX and flow cytometry. DNA-PK inhibitor combinations produced greater reductions in MTS viability in MDA-MB-231 than in MCF-7 under experimental conditions when combined with doxorubicin and 64Cu. Combination treatments generally reduced viability relative to inhibitor monotherapy, with clearer concentration dependence and stronger effects in MDA-MB-231. In the case of [64Cu]CuCl2 alone, MDA-MB-231 viability was reduced to 70–75% at 24 h, whereas several inhibitor combinations reduced it further; MCF-7 showed weaker or inconsistent potentiation. The reduction in metabolic viability became more pronounced at 72 h, particularly in MDA-MB-231 cells. Overall, the results highlight the potential of exploiting repair-pathway dependence to improve targeted radiotherapy in breast cancer.",
  "abstract_shown": true,
  "affiliations": [
    "Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania",
    "Horia Hulubei National Institute for Physics and Nuclear Engineering, 30 Reactorului Street, 077125 Magurele, Romania"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Dragoș Andrei Niculae",
      "orcid": "0009-0004-0458-6018"
    },
    {
      "affs": [
        1
      ],
      "name": "Radu Marian Șerban"
    },
    {
      "affs": [
        0
      ],
      "name": "Doina Drăgănescu"
    },
    {
      "affs": [
        1
      ],
      "name": "Dana Niculae",
      "orcid": "0000-0002-4769-843X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cqna1ec8dh4w5.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27219782",
  "fulltext_url": null,
  "id": "cqna1ec8dh4w5",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/21/9782",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-30",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/cqna1ec8dh4w5.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:54Z",
      "native_id": "10.3390/ijms27219782",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/21/9782"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "issn:1422-0067",
      "subfield": "general"
    }
  ],
  "title": "The Radiosensitizing Potential of CC-115, PIK-75 and M3814 DNA-PK Inhibitors for Breast Cancer Targeted Radiotherapy",
  "title_text": "The Radiosensitizing Potential of CC-115, PIK-75 and M3814 DNA-PK Inhibitors for Breast Cancer Targeted Radiotherapy",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T00:20:52Z",
  "url": "https://research.draconitic.com/paper/cqna1ec8dh4w5",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}