PO.TB04.03 · 肿瘤生物学
用于个体化选择腹膜癌病化疗途径和方案的人源pcVMT平台
A human pcVMT platform for personalizing chemotherapy route and regimen selection in peritoneal carcinomatosis
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
腹膜癌病(PC)是一种临床上侵袭性强的转移性疾病状态,其特征为弥漫性腹膜受累,且由于药物难以穿透间皮屏障而对全身化疗反应有限。尽管腹腔内(IP)治疗提供了一种机制上合理的替代方案,但临床医生目前缺乏与人体相关的平台来判断哪些患者将从全身治疗、IP治疗或两者联合中获益最多。为满足这一未被满足的需求,我们开发了一种双腔腹膜癌病血管化微肿瘤(pcVMT)平台,该平台重现了紧邻灌注血管网络的人体间皮衬里腹膜腔,从而实现患者特异性、途径特异性的化疗测试。pcVMT利用PC细胞系和患者来源的腹膜转移灶,支持稳定的血管灌注、完整的间皮屏障功能以及肿瘤黏附与侵袭。高分辨率共聚焦成像证实了跨多个临床样本的稳健肿瘤-基质-血管组织结构。
该平台便于测试临床相关方案,包括血管内FOLFOX、IP紫杉醇以及双向全身+IP给药,并允许在每位患者的微环境内实时可视化途径依赖的肿瘤反应。早期患者来源实验证明了个体化评估的可行性,包括成功进行IP紫杉醇给药并观察到肿瘤结构的可见变化。
通过在生理性人体腹膜模型内实现对全身、IP及联合给药策略的受控比较,pcVMT提供了一种精准肿瘤学工具,旨在为每位患者确定最有效的治疗方案和给药途径。正在进行的研究将扩大患者来源测试,并探索与临床决策的相关性,以指导PC中个体化治疗选择和未来的全身-IP联合策略。
查看英文原文 English abstract
Peritoneal carcinomatosis (PC) is a clinically aggressive metastatic disease state marked by diffuse peritoneal involvement and limited responsiveness to systemic chemotherapy due to poor penetration across the mesothelial barrier. Although intraperitoneal (IP) therapy offers a mechanistically rational alternative, clinicians currently lack human-relevant platforms to determine which patients will benefit most from systemic therapy, IP therapy, or a combination of both.To address this unmet need, we developed a dual-chamber peritoneal carcinomatosis vascularized micro-tumor (pcVMT) platform that recreates a human mesothelial-lined peritoneal cavity adjacent to a perfused vascular network, enabling patient-specific, route-specific chemotherapy testing. The pcVMT supports stable vascular perfusion, intact mesothelial barrier function, and tumor adhesion and invasion using both PC cell lines and patient-derived peritoneal metastases. High-resolution confocal imaging confirms robust tumor-stromal-vascular organization across multiple clinical samples.The platform facilitates testing of clinically relevant regimens, including vascular FOLFOX, IP paclitaxel, and bidirectional systemic+IP delivery, and permits real-time visualization of route-dependent tumor responses within each patient's microenvironment. Early patient-derived experiments demonstrate feasibility of individualized assessment, including successful IP paclitaxel administration with observable changes in tumor architecture.By enabling controlled comparison of systemic, IP, and combined delivery strategies within a physiologic human peritoneal model, the pcVMT provides a precision-oncology tool designed to identify the most effective therapy and delivery route for each patient. Ongoing studies will expand patient-derived testing and explore correlations with clinical decision-making to guide personalized treatment selection and future systemic-IP combination strategies in PC.
利益披露 Disclosure
S. J. Hachey, None..
V. K. Radhakrishnan, None..
F. Tajik, None..
M. Roman, None..
C. C. W. Hughes, None.