CLIN CANCER RES:去甲基化治疗HPV相关头颈部肿瘤

2017-12-08 MedSci MedSci原创

在HPV相关头颈部鳞状细胞癌(HNSCC)中DNA甲基化对HPV肿瘤基因表达,肿瘤细胞增殖和生存具有重要意义。CLIN CANCER RES近期发表了一篇文章,研究DNA去甲基化药物5-aza在临床前模型中对HPV相关头颈部鳞状细胞癌的作用并探索其作为靶向疗法治疗HPV+HNSCC患者的可行性。

在HPV相关头颈部鳞状细胞癌(HNSCC)中DNA甲基化对HPV肿瘤基因表达,肿瘤细胞增殖和生存具有重要意义。CLIN CANCER RES近期发表了一篇文章,研究DNA去甲基化药物5-aza在临床前模型中对HPV相关头颈部鳞状细胞癌的作用并探索其作为靶向疗法治疗HPV+HNSCC患者的可行性。

作者使用HNSCC细胞系研究其对5-aza治疗的敏感性,使用异种移植鼠模型在体内研究5-aza活性。最后还分析了临床试验患者的肿瘤标本以鉴定5-aza治疗在HPV+HNSCC患者中的活性。临床试验及实验室数据表明5-aza可以诱导HPV+HNSCC肿瘤细胞生长抑制剂细胞凋亡。5-aza降低HPV基因表达,稳定p53基因,在HNSCC细胞和肿瘤中诱导p53依赖的细胞凋亡。5-aza抑制HPV+HNSCC基质金属蛋白酶(MMP)的表达和活性,在某些HPV+头颈部肿瘤细胞中活化IFN反应,在异种移植模型中抑制HPV+肿瘤侵入血管的能力。

文章最后认为,5-aza可以为HPV相关头颈部鳞状细胞肺癌提供有效的治疗,可以作为标准细胞毒疗法的替代选择。

原始出处:
Asel Biktasova,Michael Hajek,et al.Demethylation Therapy as a Targeted Treatment for Human Papillomavirus-Associated Head and Neck Cancer.CLIN CANCER RES.December 2017 doi:10.1158/1078-0432.CCR-17-1438

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    2017-12-10 wshxjq
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