Xu Chao, Wang Bohong, Xu Tao, Lv Yao, Pan Xiani, Zhao Xiangmao, Tan Feng, Sheng Hansong, Yu Lisheng
Department of Neurosurgery, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China.
Med Oncol. 2025 Apr 29;42(6):186. doi: 10.1007/s12032-025-02734-0.
Resistance frequently arises when treating medulloblastoma (MB) patients with Vismodegib, markedly shortening their survival time. Consequently, the urgent problem to be solved is the discovery of a drug that can synergize with Vismodegib to improve its resistance in patients and enhance its efficacy. To validate the feasibility and efficacy of combining EZH2 (Enhancer of zeste homolog 2) inhibitor (EZH2i) with Vismodegib. A comprehensive assessment of their individual and combined effects on MB cell proliferation, migration, and invasion capabilities was conducted. The promising potential of EZH2i in inhibiting MB cell growth, migration and invasion was exhibited when used alone. Furthermore, when combined with Vismodegib, the inhibitory effect on MB was significantly potentiated. This synergy was further confirmed by SynergyFinder analysis, which revealed a remarkable highest single-agent score of 14.85 for the GSK126 and Vismodegib combination. Importantly, the enhanced efficacy of the combined EZH2i and Vismodegib therapy in suppressing tumor growth was also verified by the xenograft experiments in vivo. In summary, the combined use of EZH2i and Vismodegib demonstrated a remarkable synergistic effect in suppressing MB growth, presenting a promising treatment option for MB patients who had become resistant to Vismodegib.
在使用维莫德吉治疗髓母细胞瘤（MB）患者时，耐药性经常出现，这显著缩短了他们的生存时间。因此，亟待解决的问题是发现一种能够与维莫德吉协同作用，提高患者对其耐药性并增强其疗效的药物。为了验证EZH2（zeste同源物2增强子）抑制剂（EZH2i）与维莫德吉联合使用的可行性和疗效，对它们单独及联合使用对MB细胞增殖、迁移和侵袭能力的影响进行了全面评估。单独使用时，EZH2i在抑制MB细胞生长、迁移和侵袭方面显示出有前景的潜力。此外，与维莫德吉联合使用时，对MB的抑制作用显著增强。SynergyFinder分析进一步证实了这种协同作用，该分析显示GSK126与维莫德吉联合使用时的最高单药评分达到了显著的14.85。重要的是，体内异种移植实验也证实了EZH2i与维莫德吉联合治疗在抑制肿瘤生长方面增强的疗效。总之，EZH2i与维莫德吉联合使用在抑制MB生长方面显示出显著的协同效应，为对维莫德吉产生耐药性的MB患者提供了一种有前景的治疗选择。
