文章：

针对伯基特淋巴瘤的双重靶向策略：EZH2降解与EGFR/HER2抑制协同增强疗效

Dual Targeting of EZH2 Degradation and EGFR/HER2 Inhibition for Enhanced Efficacy against Burkitt’s Lymphoma

原文发布日期：8 September 2023

DOI: 10.3390/cancers15184472

类型: Article

开放获取: 是

英文摘要：

EZH2, a histone methyltransferase, contributes significantly to cancer cell survival and proliferation. Although various EZH2 inhibitors have demonstrated promise in treating lymphoma, they have not fully managed to curb lymphoma cell proliferation despite effective reduction of the H3K27me3 mark. We used MS1943, an EZH2 selective degrader, which successfully diminishes EZH2 levels in lymphoma cells. Additionally, lapatinib, a dual inhibitor of the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) tyrosine kinases, targets a receptor protein that regulates cell growth and division. The overexpression of this protein is often observed in lymphoma cells. Our study aims to combine these two therapeutic targets to stimulate apoptosis pathways and potentially suppress Burkitt’s lymphoma cell survival and proliferation in a complementary and synergistic manner. We observed that a combination of MS1943 and lapatinib induced apoptosis in Daudi cells and caused cell cycle arrest at the S and G2/M phases in both Ramos and Daudi cells. This strategy, using a combination of MS1943 and lapatinib, presents a promising therapeutic approach for treating lymphoma and potentially Burkitt’s lymphoma.

摘要翻译： 

EZH2作为一种组蛋白甲基转移酶，在癌细胞的存活与增殖过程中发挥重要作用。尽管多种EZH2抑制剂在淋巴瘤治疗中展现出潜力，但即使能有效降低H3K27me3标记水平，仍未能完全抑制淋巴瘤细胞的增殖。本研究采用EZH2选择性降解剂MS1943，成功降低了淋巴瘤细胞中的EZH2水平。同时，拉帕替尼作为表皮生长因子受体（EGFR）和人表皮生长因子受体2（HER2）酪氨酸激酶的双重抑制剂，靶向调控细胞生长分裂的受体蛋白——该蛋白在淋巴瘤细胞中常出现过表达现象。本研究旨在通过联合靶向这两种治疗靶点，以互补协同的方式激活细胞凋亡通路，从而抑制伯基特淋巴瘤细胞的存活与增殖。实验结果显示，MS1943与拉帕替尼联合用药能诱导Daudi细胞发生凋亡，并使Ramos和Daudi细胞的细胞周期阻滞于S期和G2/M期。这种联合用药策略为淋巴瘤特别是伯基特淋巴瘤的治疗提供了具有前景的新途径。

原文链接：

Dual Targeting of EZH2 Degradation and EGFR/HER2 Inhibition for Enhanced Efficacy against Burkitt’s Lymphoma