肿瘤低氧与放疗和化疗的耐药性相关。在头颈部鳞状细胞癌（HNSCC）中，奈莫唑，一种模拟氧气的药物，与放疗（RT）结合使用，能够提高部分低氧肿瘤患者的局部控制（LRC），但不清楚这是否也适用于放疗化疗（RCTx）。在这里，我们研究了奈莫唑与RCTx联合应用对HNSCC异种移植瘤的影响，并探索了其有针对性使用的分子生物标志物。放射治疗采用每周一次顺铂的方式，每次放疗次数为30次，共持续6周。奈莫唑在每次放疗之前应用，开始于第一次放疗或第十次放疗后。通过放疗后的局部持久控制来量化RCTx与或不加入奈莫唑的效果。为了进行组织学评价和靶向基因表达分析，肿瘤在未经处理或接受十次放疗后被切取。利用定量图像分析，确定了微环境参数。奈莫唑与RCTx联合应用在两个肿瘤模型中显著改善了持久局部控制，并在另外两个模型中显示了潜在的改善。在这四个模型中，十次放疗后的RCTx单独治疗可显著减少噻佐嗪低氧体积（pHV）。我们的结果表明，如果在RCTx过程中降低低氧状况，奈莫唑与RCTx的联合使用可能改善TCR与单独RCTx相比，但需要进一步的实验证明这种关联性。差异基因表达分析鉴定出12个基因作为RCTx反应的潜在标志。在接受初级RCTx治疗的HNSCC患者中评估时，这些基因对LRC具有预测性。奈莫唑与RCTx联合应用改善了HNSCC异种移植瘤中的局部肿瘤控制，但并非所有异种移植瘤都有所改善。我们确定了具有潜力转化为HNSCC患者的预后生物标志物。© 2023. BioMed Central Ltd., part of Springer Nature.

Tumor hypoxia is associated with resistance to radiotherapy and chemotherapy. In head and neck squamous cell carcinoma (HNSCC), nimorazole, an oxygen mimic, combined with radiotherapy (RT) enabled to improve loco-regional control (LRC) in some patients with hypoxic tumors but it is unknown whether this holds also for radiochemotherapy (RCTx). Here, we investigated the impact of nimorazole combined with RCTx in HNSCC xenografts and explored molecular biomarkers for its targeted use.Irradiations were performed with 30 fractions in 6 weeks combined with weekly cisplatin. Nimorazole was applied before each fraction, beginning with the first or after ten fractions. Effect of RCTx with or without addition of nimorazole was quantified as permanent local control after irradiation. For histological evaluation and targeted gene expression analysis, tumors were excised untreated or after ten fractions. Using quantitative image analysis, micromilieu parameters were determined.Nimorazole combined with RCTx significantly improved permanent local control in two tumor models, and showed a potential improvement in two additional models. In these four models, pimonidazole hypoxic volume (pHV) was significantly reduced after ten fractions of RCTx alone. Our results suggest that nimorazole combined with RCTx might improve TCR compared to RCTx alone if hypoxia is decreased during the course of RCTx but further experiments are warranted to verify this association. Differential gene expression analysis revealed 12 genes as potential for RCTx response. When evaluated in patients with HNSCC who were treated with primary RCTx, these genes were predictive for LRC.Nimorazole combined with RCTx improved local tumor control in some but not in all HNSCC xenografts. We identified prognostic biomarkers with the potential for translation to patients with HNSCC.© 2023. BioMed Central Ltd., part of Springer Nature.