Abstract 3988: Patient-specific 3D engineered microphysiological systems to model triple-negative breast cancer chemotherapy using patient-derived xenograft (PDX) tissue

Abstract Chemotherapy efficacy and pharmacokinetics are influenced by a patient’s unique characteristics, including gender, ethnicity, age, gene expression, and disease state. Three-dimensional (3D) tissue models integrated into microfluidic devices offer a controlled and reproducible platform to study cellular responses to drugs, leveraging fluid circulation for precise quantification. These models can be tailored to individual patients through the incorporation of patient-derived xenograft (PDX) tissues, which are purified and encapsulated within biomimetic hydrogels that replicate the tumor extracellular matrix (ECM). The objective of this study was to develop a patient-specific 3D model of triple-negative breast cancer (TNBC) cultured in a self-driven, closed-capillary microfluidic device to assess chemotherapy efficacy, toxicity, and tumor microenvironment interactions in vitro. We hypothesized that integrating human TNBC PDX tissue into customized microfluidic devices would create physiologically relevant systems to study disease pathology and treatment responses in vitro. TNBC-PDX tissues were isolated to establish a cell line expressing human EpCAM with a population doubling time of 48 hours. A CC50 value of ∼10 µM was determined via flow cytometry viability assays following treatment with a 10-fold dilution series of Doxorubicin (DOX). The cells were encapsulated in 3D collagen hydrogels (0.2 wt%) and cultured in transwell (TW) dishes or microfluidic devices (DwP). These 3D TNBC-PDX models demonstrated viability, elongated morphology, and tumor-like clustering within DwP, reorganizing according to device microfeatures. When treated with 10 µM DOX, the 3D cultures in both TW and DwP conditions exhibited limited cell death, reflecting the original tumor’s drug-resistant phenotype. These findings highlight the feasibility of integrating PDX tissues into microfluidic systems to create patient-specific 3D models, offering a physiologically relevant platform for evaluating chemotherapy responses. This approach may advance personalized cancer treatment strategies by enabling in vitro assessment of drug efficacy and resistance mechanisms. Citation Format: Edgar A. Borrego, Linjie Luo, Janine Hagar-Montoya, Jose L. Perez, Paula Delgado, Khandan Keyomarsi, Sylvia L. Natividad-Diaz. Patient-specific 3D engineered microphysiological systems to model triple-negative breast cancer chemotherapy using patient-derived xenograft (PDX) tissue [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3988.