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Background <p>Head and neck squamous cell carcinoma (HNSCC) is a relevant cancer entity with two main risk factors. Human papilloma virus (HPV)-positive ones are induced by virus infection and generally have a good prognosis due to their chemo- and radiosensitivity. In contrast, HPV-negative HNSCCs are primarily caused by tobacco and alcohol abuse; patients have a poor prognosis resulting in the need of innovative targeted and combinatory treatment options. Therefore, we combined the Mre11-Rad50-Nbs1 (MRN) inhibitor Mirin with ionizing radiation (IR). Our hypothesis is that the inhibition of the cancer cells’ DNA damage response (DDR) by Mirin leads to reduced repair capacity and a radiosensitization of the cancer cells.</p> Methods <p>We investigated the effect of Mirin in combination with IR on five HPV-negative and two HPV-positive HNSCC cell lines and one primary fibroblast cell line - serving as healthy control - in several functional assays.</p> Results <p>We suggest – on the one hand - that Mirin shows a trend towards radiosensitizing effects regarding cell death, cell cycle distribution, colony formation, and deoxyribonucleic acid (DNA) damage in HPV-negative HNSCC cell lines but not in HPV-positive ones. On the other hand, the healthy control was nearly unaffected by the combinatory treatment which indicates low side effects.</p> Conclusions <p>It is useful to generate a deeper insight into the underlying cellular mechanisms of Mirin response in future studies and further validate Mirin’s potential radiosensitizing effect in HPV-negative HNSCCs.</p> Graphical abstract <p></p>

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The inhibition of the MRN complex by Mirin radiosensitizes particularly HPV-negative HNSCC cell lines

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月4日

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  • Laura S. Hildebrand,
  • Babak Pornour Mehravani,
  • Mohammed Khalifa,
  • Paula Schiller,
  • Janis Langkrär,
  • Tina Jost,
  • Rainer Fietkau,
  • Luitpold V. Distel

摘要

Background

Head and neck squamous cell carcinoma (HNSCC) is a relevant cancer entity with two main risk factors. Human papilloma virus (HPV)-positive ones are induced by virus infection and generally have a good prognosis due to their chemo- and radiosensitivity. In contrast, HPV-negative HNSCCs are primarily caused by tobacco and alcohol abuse; patients have a poor prognosis resulting in the need of innovative targeted and combinatory treatment options. Therefore, we combined the Mre11-Rad50-Nbs1 (MRN) inhibitor Mirin with ionizing radiation (IR). Our hypothesis is that the inhibition of the cancer cells’ DNA damage response (DDR) by Mirin leads to reduced repair capacity and a radiosensitization of the cancer cells.

Methods

We investigated the effect of Mirin in combination with IR on five HPV-negative and two HPV-positive HNSCC cell lines and one primary fibroblast cell line - serving as healthy control - in several functional assays.

Results

We suggest – on the one hand - that Mirin shows a trend towards radiosensitizing effects regarding cell death, cell cycle distribution, colony formation, and deoxyribonucleic acid (DNA) damage in HPV-negative HNSCC cell lines but not in HPV-positive ones. On the other hand, the healthy control was nearly unaffected by the combinatory treatment which indicates low side effects.

Conclusions

It is useful to generate a deeper insight into the underlying cellular mechanisms of Mirin response in future studies and further validate Mirin’s potential radiosensitizing effect in HPV-negative HNSCCs.

Graphical abstract