背景 表观遗传学也许比组织病理学更准确地预测脑膜瘤患者的治疗敏感性和临床病程。尽管如此，针对这些肿瘤的药物治疗研究中，表观遗传机制的作用还未得到充分研究。我们对脑膜瘤表观遗传学的生物分子洞察和潜在治疗研究引发了我们对脑膜瘤中表观遗传抑制的调查。方法 我们使用一个含有139种抑制剂的表观遗传抑制剂库，对一个由43个肿瘤组成的队列进行筛选，以评估相关脑膜瘤亚组对表观遗传抑制的敏感性。该队列由5株细胞系和38个通过手术直接培养的肿瘤组成；患者平均年龄为56.6岁，标准差为13.9。肿瘤分为：38个原发肿瘤，5个复发肿瘤；33个来自女性，10个来自男性；32个为1级肿瘤，10个为2级肿瘤，1个为3级肿瘤。结果 与之前我们的结果一致，组蛋白脱乙酰酶抑制剂（HDACi）是最有效的类别。泛素连接酶H2显著降低了36个肿瘤的细胞活力；41个肿瘤对某些HDACi具有显著敏感性。对G9a抑制和Jumonji结构域抑制的敏感性也在整个队列中显著降低；对泛素连接酶H2失去敏感性的肿瘤仍然对G9a抑制或Jumonji结构域抑制保持敏感性。G9a和HDAC抑制的敏感性随肿瘤分级增加而增加；肿瘤反应与性别无关。复发肿瘤和原发肿瘤之间以及有过放射治疗和无放射治疗之间的差异很少。结论 目前只有少量研究探讨了针对脑膜瘤的表观遗传机制治疗的疗效，这样使得表观遗传抑制在临床上的应用价值尚不明确。我们的结果表明，表观遗传抑制是脑膜瘤药物治疗的一个可开发领域。版权所有， Thieme.

Background  Epigenetics may predict treatment sensitivity and clinical course for patients with meningiomas more accurately than histopathology. Nonetheless, targeting epigenetic mechanisms is understudied for pharmacotherapeutic development for these tumors. The bio-molecular insights and potential therapeutic development of meningioma epigenetics led us to investigate epigenetic inhibition in meningiomas. Methods  We screened a 43-tumor cohort using a 139-compound epigenetic inhibitor library to assess sensitivity of relevant meningioma subgroups to epigenetic inhibition. The cohort was composed of 5 cell lines and 38 tumors cultured directly from surgery; mean patient age was 56.6 years ± 13.9 standard deviation. Tumor categories: 38 primary tumors, 5 recurrent; 33 from females, 10 from males; 32 = grade 1; 10 = grade 2; 1 = grade 3. Results  Consistent with our previous results, histone deacetylase inhibitors (HDACi) were the most efficacious class. Panobinostat significantly reduced cell viability in 36 of 43 tumors; 41 tumors had significant sensitivity to some HDACi. G9a inhibition and Jumonji-domain inhibition also significantly reduced cell viability across the cohort; tumors that lost sensitivity to panobinostat maintained sensitivity to either G9a or Jumonji-domain inhibition. Sensitivity to G9a and HDAC inhibition increased with tumor grade; tumor responses did not separate by gender. Few differences were found between recurrent and primary tumors, or between those with prior radiation versus those without. Conclusions  Few efforts have investigated the efficacy of targeting epigenetic mechanisms to treat meningiomas, making the clinical utility of epigenetic inhibition largely unknown. Our results suggest that epigenetic inhibition is a targetable area for meningioma pharmacotherapy.Thieme. All rights reserved.