Construction Of Multicellular Tumor-On-A-Chip Models for Ovarian Cancer Research

IF 11.6 1区工程技术 Q1 ENGINEERING, MULTIDISCIPLINARY

Engineering Pub Date : 2025-08-27 DOI:10.1016/j.eng.2025.08.028

Jiexian Ye, Hao Lin, Zilin Zhang, Shihui Xu, Feili Yang, Xuemei Zhuansun, Feng Ji, Yusha Zhang, Yuxin Zhu, Jing Zhang, Zaozao Chen, Zhongze Gu, Yang Shen

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引用次数: 0

Abstract

Ovarian cancer remains a highly lethal gynecologic malignancy. Early diagnosis poses significant challenges, and the five-year survival rate is consistently below 45%. Current standard-of-care combines surgical resection with platinum-based chemotherapy. Emerging therapeutic modalities like chimeric antigen receptor-T (CAR-T) therapy show promise, though they face efficacy constraints due to tumor heterogeneity and immunosuppressive microenvironments. Conventional models including two-dimensional (2D) cultures and patient-derived xenografts are increasingly supplanted by organoid and tumor-on-a-chip technologies due to intrinsic limitations and poor clinical translatability. This study established multiple tumor-on-a-chip platforms derived from ovarian cancer organoids and conducted systematic in vitro drug sensitivity screening. Furthermore, by utilizing patient-derived organoids to engineer multicellular dynamic microenvironments, we achieved one of the extremely limited evaluations of CAR-T efficacy against solid tumors within ovarian cancer microfluidic systems. This work establishes an enhanced preclinical platform to advance therapeutic screening and personalized treatment development.

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构建卵巢癌多细胞肿瘤芯片模型

卵巢癌是一种高度致命的妇科恶性肿瘤。早期诊断面临重大挑战，5年生存率一直低于45%。目前的标准治疗将手术切除与铂基化疗相结合。嵌合抗原受体- t （CAR-T）治疗等新兴治疗方式显示出希望，尽管由于肿瘤异质性和免疫抑制微环境，它们面临疗效限制。由于固有的局限性和较差的临床可翻译性，包括二维（2D）培养和患者来源的异种移植在内的传统模型越来越多地被类器官和肿瘤芯片技术所取代。本研究建立了多种来源于卵巢癌类器官的肿瘤芯片平台，并进行了系统的体外药敏筛选。此外，通过利用患者来源的类器官来设计多细胞动态微环境，我们实现了卵巢癌微流控系统中CAR-T对实体瘤的疗效的极其有限的评估之一。这项工作建立了一个增强的临床前平台，以推进治疗筛选和个性化治疗的发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Engineering Environmental Science-Environmental Engineering

自引率

1.60%

发文量

335

审稿时长

35 days

期刊介绍： Engineering, an international open-access journal initiated by the Chinese Academy of Engineering (CAE) in 2015, serves as a distinguished platform for disseminating cutting-edge advancements in engineering R&D, sharing major research outputs, and highlighting key achievements worldwide. The journal's objectives encompass reporting progress in engineering science, fostering discussions on hot topics, addressing areas of interest, challenges, and prospects in engineering development, while considering human and environmental well-being and ethics in engineering. It aims to inspire breakthroughs and innovations with profound economic and social significance, propelling them to advanced international standards and transforming them into a new productive force. Ultimately, this endeavor seeks to bring about positive changes globally, benefit humanity, and shape a new future.