A human pcVMT platform for personalizing chemotherapy route and regimen selection in peritoneal carcinomatosis

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.