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针对骨髓化疗来逆转前列腺癌治疗耐药性

Christina Guo^1,2, Adam Sharp^1,2, Bora Gurel¹

¹The Institute of Cancer Research, London, UK.

|October 16, 2023

概括

在前列腺癌中抑制骨髓细胞招募逆转了治疗耐药性. 针对骨髓细胞化疗减少了瘤炎症,改善了转移性抵抗割的前列腺癌患者的治疗结果.

科学领域:

癌症学
免疫学
泌尿外科

背景情况:

在各种癌症中,炎症,特别是高中性细胞与淋巴细胞比率表明的骨髓扩张,与生存率低下和治疗耐药性有关.
骨髓炎在推动前列腺癌进展和治疗耐药性的作用尚不清楚.

研究的目的:

调查是否抑制骨髓细胞化学反应可以减少瘤引起的骨髓细胞炎症,并克服转移性抵抗割的前列腺癌 (CRPC) 的治疗耐药性.
确定针对CXCR2连体是否可以逆转CRPC对雄激素受体信号抑制剂 (ARSI) 的耐药性.

主要方法:

在ARSI耐药的转移性CRPC患者中进行了一项结合CXCR2抑制剂 (AZD5069) 的概念验证临床试验.
评估了组合治疗对循环中性粒细胞水平,内髓细胞透和临床结果 (生化和放射反应) 的影响.
与瘤髓细胞透和老化相关的mRNA,包括CXCR2配体的表达相关的血中中微粒细胞与淋巴细胞的比率.

主要成果:

组合疗法耐受良好,没有剂量限制性毒性.
治疗减少了循环中性粒细胞,减少了内髓细胞透 (CD11b+HLA-DRloCD15+CD14-),并在一组患者中显示出持久的临床益处.
在接受CXCR2抑制剂和恩扎胺治疗的患者中观察到的生化和放射性反应.

结论:

与衰老相关的骨髓炎可以推动转移性CRPC的进展和对雄激素受体阻断的抵抗.
通过CXCR2阻断抑制骨髓化疗是一种有前途的策略,可以逆转CRPC患者的治疗耐药性.
在其他癌症类型中进行进一步的研究.

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