Yuan Zhen, Zhou Huimei, Cao Dongyan, Yang Jiaxin, Liu Qian
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
J Gynecol Oncol. 2025 May;36(3):e40. doi: 10.3802/jgo.2025.36.e40. Epub 2024 Oct 21.
The study aimed to establish humanized patient-derived xenograft (PDX) mouse models of ovarian clear cell carcinoma (OCCC) and evaluate their therapeutic responses.
PDX models and their humanized counterparts (CD34+ humanized PDX models) derived from the same tumor source were developed, and the therapeutic responses were compared between the models.
Treatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor significantly reduced tumor size in traditional OCCC PDX models (p=0.021). Although differences in tumor growth between traditional PDX models and humanized PDX models were observed, they were not statistically significant (p=0.438). However, treatment effects of PI3K inhibitor differed significantly between conventional and humanized mice (p=0.006). In the Humanized PDX cohort, both programmed cell death protein-1 antibody monotherapy and PI3K inhibitor treatment slowed tumor growth relative to controls, with a synergistic effect noted during the latter part of the study, though these effects were not statistically significant.
This pioneering study successfully develop a humanized PDX model for OCCC, highlighting differential responses to treatments compared to conventional PDX models.
本研究旨在建立卵巢透明细胞癌（OCCC）的人源化患者来源异种移植（PDX）小鼠模型，并评估其治疗反应。
建立了源自同一肿瘤源的PDX模型及其人源化对应模型（CD34+人源化PDX模型），并比较了模型之间的治疗反应。
用磷脂酰肌醇3-激酶（PI3K）抑制剂治疗可显著减小传统OCCC PDX模型中的肿瘤大小（p = 0.021）。虽然观察到传统PDX模型与人源化PDX模型之间肿瘤生长存在差异，但差异无统计学意义（p = 0.438）。然而，PI3K抑制剂的治疗效果在传统小鼠与人源化小鼠之间存在显著差异（p = 0.006）。在人源化PDX队列中，程序性细胞死亡蛋白1抗体单药治疗和PI3K抑制剂治疗相对于对照组均减缓了肿瘤生长，在研究后期观察到协同效应，尽管这些效应无统计学意义。
这项开创性研究成功建立了OCCC的人源化PDX模型，突出了与传统PDX模型相比对治疗的不同反应。
