文章：

CREBBP突变肿瘤对HDAC抑制剂的优先敏感性

Preferential sensitivity to HDAC inhibitors in tumors with CREBBP mutation 

原文发布日期：2019-05-09 

英文摘要：

Mutations in the gene encoding for the histone acetyltransferase (HAT) CREBBP are common driver events in multiple types of human cancer, such as small cell lung cancer (SCLC) or Sonic Hedgehog medulloblastoma (SHH MB). Therefore, therapeutic options targeting such alterations are highly desired. We used human cell lines from SCLC as well as primary mouse tumor cells and genetically engineered mouse models for SHH MB to test treatment options with histone deacetylase inhibitors (HDACi) in CREBBP wild-type and mutated tumors. In contrast to CREBBP wild-type SCLC cells, CREBBP-mutated SCLC cells showed significantly lower IC50 values after treatment with HDACi. In addition, both in vitro and in vivo, HDACi had significant effects on cell proliferation of SHH-driven tumor MB cells harboring a CREBBP-mutation as compared to CREBBP wild-type controls. These data suggest that HDACi may serve as an additional therapeutic option for patients suffering from tumors driven by CREBBP mutations. 

摘要翻译： 

编码组蛋白乙酰转移酶（HAT）CREBBP的基因突变是多种人类癌症（如小细胞肺癌/SCLC或音猬因子髓母细胞瘤/SHH MB）中常见的驱动事件。因此，针对此类基因改变的治疗方案备受期待。我们采用小细胞肺癌人类细胞系、原代小鼠肿瘤细胞以及SHH MB基因工程小鼠模型，测试了组蛋白去乙酰化酶抑制剂（HDACi）对CREBBP野生型与突变型肿瘤的疗效。研究显示：与CREBBP野生型SCLC细胞相比，经HDACi治疗后，CREBBP突变型SCLC细胞的半数抑制浓度（IC50）值显著降低。此外，在体外和体内实验中，HDACi对携带CREBBP突变的SHH驱动型髓母细胞瘤的细胞增殖抑制作用均显著强于CREBBP野生型对照组。这些数据表明，HDACi或可为CREBBP突变驱动型肿瘤患者提供一种新的治疗选择。

原文链接：

Preferential sensitivity to HDAC inhibitors in tumors with CREBBP mutation