在慢性淋巴细胞白血病中,与抗生素药物联合使用的selinexor的抗瘤活性

在慢性淋巴细胞白血病中,与抗生素药物联合使用的selinexor的抗瘤活性

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Candida Vitale^1,2, Valentina Griggio^1,2, Maria Todaro^1,2

¹University Division of Hematology, A.O.U. Città della Salute e della Scienza di Torino, 10126, Turin, Italy.

Scientific reports

|October 7, 2023

概括

这项研究表明,与其他药物相结合的selinexor显著增强了慢性淋巴细胞白血病 (CLL) 的抗癌效应. 这些组合显示出协同性细胞毒性,为这种无法治愈的血液癌症提供了潜在的新疗法.

科学领域:

血液学血液学血液学
在瘤学瘤学.
药理学药理学是指药理学的学科.

背景情况:

慢性淋巴细胞白血病 (CLL) 仍然是一个无法治愈的血液恶性瘤,尽管治疗方面取得了进展.
作为口服XPO1抑制剂的Selinexor在包括CLL在内的各种血液癌症中表现出活性.

研究的目的:

为了评估在CLL中与化疗 (fludarabine,bendamustine) 或idelalisib (PI3Kδ抑制剂) 结合使用的selinexor的抗瘤作用.
研究这些组合的协同细胞毒性作用和分子机制.

主要方法:

在实验室中评估基于selinexor的药物组合的CLL细胞活力.
药物协同作用在有保护性树皮细胞的情况下的评估.
对分子点的分析,包括FOXO3A和IkBα.
在小鼠体内研究,以评估塞林克索和伊德拉利西布组合的抗瘤疗效.

主要成果:

与单一药物相比,含有塞利尼克索的组合药物显著降低了CLL细胞活力,表明了协同性细胞毒性.
即使存在保护性树皮细胞,也观察到协同效应.
结合塞林尼克索和伊德拉利西布显示,增强了瘤抑制剂FOXO3A和IkBα的调节.
在体内研究证实了selinexor-idelalisib组合的强化抗瘤作用.

结论:

在CLL中,Selinexor在与化疗或idelalisib相结合时表现出协同的细胞毒性作用.
塞林克索和伊德拉利西布的组合显示出有希望的临床前疗效,并需要进一步研究CLL治疗.
准XPO1和PI3Kδ通路为CLL提供了一个潜在的治疗策略.

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