TY - JOUR
KW - microfluidic
KW - organ on chip
KW - pancreatic cancer
KW - patient derived organoids
KW - Tumor Microenvironment
AU - Darbaz Adnan
AU - Natan Roberto de Barros
AU - Luca S. Santovito
AU - Xuhong Cheng
AU - Kristi M. Lawrence
AU - Mariah K. Barnett
AU - Martine D. Boetto
AU - Neal Mehta
AU - Ajaypal Singh
AU - Lin Cheng
AU - Xiangsheng Huang
AU - Faraz Bishehsari
AB - Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy. Current conventional chemotherapeutics are inadequate in controlling the disease; hence, there is an urgent need for precision medicine. Ex vivo models that replicate the tumor and its microenvironment can advance precision medicine in PDAC. Patient-derived organoids (PDOs) offer a promising solution by retaining the functional features of the tumor, allowing for individualized study of cancer biology and drug response. However, PDOs fall short in replicating the tumor microenvironment (TME), which includes various stromal and immune cells influencing tumor growth and chemoresistance. We hypothesize that combining PDO technology with organ-on-a-chip (OoC) systems can enhance ex vivo cancer modeling. Here, we develop a patient-derived platform by incorporating PDOs with key components of the TME (fibroblasts, endothelial cells, and immune cells) within a microfluidic system. This OoC model represents the crosstalk between cancer and stroma observed in PDAC in vivo. Targeting the stroma improves the effectiveness of standard chemotherapy in this OoC. Further, using this platform, we are able to model and assess the efficacy of immune checkpoint blockade for T cell cytotoxicity in PDAC. The OoC provides a pathophysiologically applicable system to support future investigations aimed at utilizing precision medicine and testing therapeutics in PDAC.
BT - Advanced Science
DO - 10.1002/advs.202508934
IS - n/a
LA - en
N2 - Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy. Current conventional chemotherapeutics are inadequate in controlling the disease; hence, there is an urgent need for precision medicine. Ex vivo models that replicate the tumor and its microenvironment can advance precision medicine in PDAC. Patient-derived organoids (PDOs) offer a promising solution by retaining the functional features of the tumor, allowing for individualized study of cancer biology and drug response. However, PDOs fall short in replicating the tumor microenvironment (TME), which includes various stromal and immune cells influencing tumor growth and chemoresistance. We hypothesize that combining PDO technology with organ-on-a-chip (OoC) systems can enhance ex vivo cancer modeling. Here, we develop a patient-derived platform by incorporating PDOs with key components of the TME (fibroblasts, endothelial cells, and immune cells) within a microfluidic system. This OoC model represents the crosstalk between cancer and stroma observed in PDAC in vivo. Targeting the stroma improves the effectiveness of standard chemotherapy in this OoC. Further, using this platform, we are able to model and assess the efficacy of immune checkpoint blockade for T cell cytotoxicity in PDAC. The OoC provides a pathophysiologically applicable system to support future investigations aimed at utilizing precision medicine and testing therapeutics in PDAC.
EP - e08934
T2 - Advanced Science
TI - A Patient-Derived Organ-on-Chip Platform for Modeling the Tumor Microenvironment and Drug Responses in Pancreatic Cancer
UR - https://onlinelibrary.wiley.com/doi/abs/10.1002/advs.202508934
VL - n/a
Y2 - 2026-01-30
SN - 2198-3844
ER -