PO.TB04.08 · 肿瘤生物学
开发用于卵巢癌临床前评估的患者来源类器官和异种移植模型
Developing patient-derived organoid and xenograft models for preclinical assessment in ovarian cancer
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：卵巢癌（OC）是一种高度致命的恶性肿瘤，其特点是诊断时多为晚期、肿瘤异质性显著以及总体预后不良。OC的临床前模型，包括患者来源类器官（PDO）和异种移植（PDX），已被研究用于药物开发和精准医学。在本研究中，我们建立了OC PDO和PDX模型。
方法：在手术过程中从多个部位（卵巢、大网膜、膈肌和腹膜）或腹水中采集肿瘤组织。组织解离后，将单细胞包埋于基底膜提取物中进行PDO培养，并将其经卵巢囊内或皮下注射至免疫缺陷小鼠（NOD/Shi-scid IL-2Rγ null）以生成PDX。PDO成功培养超过五代，并使用CellTiter-Glo 3D活力测定法对14种药物（包括铂类药物、紫杉烷类、拓扑异构酶抑制剂和PARP抑制剂）进行了药物筛选。每周监测PDX肿瘤生长三次，并分析达到100 mm³的时间点。
结果：从14名具有不同组织学和遗传学特征的晚期OC患者中成功建立了共18个PDO。药物筛选显示反应范围各异，曲线下面积介于0.29至1.00之间，尤其对铂类药物和PARP抑制剂如此。OC PDX模型在34名患者中的9名（26.5%）成功建立。总体而言，达到100 mm³肿瘤生长的时间在卵巢囊内模型中比皮下模型更短，平均时间分别为90.3天（n = 4）和149.8天（n = 9）。值得注意的是，随着连续传代，肿瘤形成加速，提示后代具有更高的移植效率和生长动力学。
结论：我们成功开发了保留肿瘤异质性的OC PDO和PDX模型。这些模型能够对肿瘤生物学进行详细研究，为开发新型治疗策略提供关键见解。本研究由韩国政府（MSIT）资助的国家研究基金会（NRF）生物与医学技术开发项目支持：RS-2025-19542979，RS-2025-25437292
查看英文原文 English abstract
Background: Ovarian cancer (OC) is a highly lethal malignancy, characterized by late-stage diagnosis, marked tumor heterogeneity, and poor overall prognosis. Preclinical models of OCs, including patient-derived organoids (PDO) and xenografts (PDX), has been investigated for drug development and precision medicine. In this study, we established OC PDOs and PDX models
Methods: Tumor tissue were collected from multiple sites (ovary, omentum, diaphragm, and peritoneum) or ascites during surgery. After tissue dissociation, single cells were embedded in basement membrane extract for PDO culture and injected either intrabursally or subcutaneously into immunodeficient mice (NOD/Shi-scid IL-2Rν null ) to generate PDXs. PDOs were successfully cultured beyond five passage, and drug screening across 14 drugs including platinum-based agents, taxanes, topoisomerase inhibitors, and PARP inhibitors was performed using the CellTiter-Glo 3D viability assay. PDXs tumor growth were monitored three times a week, and analyzed the time points to reach 100 mm 3 .
Results: A total of 18 PDOs were successfully established from 14 advanced-stage OC patients with diverse histological and genetical characteristics. Drug screening demonstrated a variable range of responses with the area under the curve ranging from 0.29 to 1.00, especially to platinum-based drugs and PARP inhibitors. The OC PDX model was successfully established in 9 (26.5%) out of 34 patients. Overall, the duration until 100 mm 3 tumor growth was shorter in intrabursal models compared to subcutaneous models with mean times of 90.3 days (n = 4) and 149.8 days (n = 9), respectively. Notably, tumor formation accelerated with successive passages, suggesting enhanced engraftment efficiency and growth kinetics in later generations.
Conclusions: We successfully developed OC PDO and PDX models that preserve tumor heterogeneity. These models enable detailed investigation of tumor biology offering critical insights for the development of novel treatment strategies. This research was supported by the Bio&Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT): RS-2025-19542979, RS-2025-25437292
利益披露 Disclosure
C. Lee, None..
J. Heo, None..
J. Jeong, None..
H. Lee, None..
J. Park, None..
W. Choi, None..
S. Park, None..
Y. Woo, None..
M. Lim, None..
S. Kong, None.