Stepchenko A G, Ilyin Yu V, Georgieva S G, Pankratova E V
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
Dokl Biol Sci. 2025 Feb;520(1):60-63. doi: 10.1134/S0012496624600635. Epub 2025 Jan 31.
Primary drug resistance of tumor cells or resistance acquired during treatment is among the main factors that significantly limit the efficacy of antitumor chemotherapy, along with severe side effects depending on the drug dose. To increase the efficacy, chemotherapeutics can be used in combination with substances that modulate the functions of cell signaling pathways. In this work, the substance XMU-MP-1, an inhibitor of key MST1/2 kinases of the Hippo signaling pathway, was shown to enhance the antitumor activity of two genotoxic chemotherapeutics, etoposide and cisplatin, against Namalwa Burkitt's B-cell lymphoma cells. XMU-MP-1 increased the cytotoxicity of the agents and significantly reduced their CTD. The drug efficacy is therefore possible to increase significantly, and a therapeutic effect might be achieved at a lower drug concentration to reduce the likelihood of life-threatening side effects.
肿瘤细胞的原发性耐药性或治疗期间获得的耐药性是显著限制抗肿瘤化疗疗效的主要因素之一，同时还存在取决于药物剂量的严重副作用。为提高疗效，化疗药物可与调节细胞信号通路功能的物质联合使用。在这项研究中，Hippo信号通路关键MST1/2激酶的抑制剂XMU-MP-1被证明可增强两种基因毒性化疗药物依托泊苷和顺铂对Namalwa伯基特B细胞淋巴瘤细胞的抗肿瘤活性。XMU-MP-1增加了药物的细胞毒性并显著降低了其CTD。因此有可能显著提高药物疗效，并且可以在较低药物浓度下实现治疗效果，以降低危及生命的副作用发生的可能性。
