02393nas a2200337   4500000000100000000000100001008004100002653001700043653001800060653002200078653003000100653002700130100001700157700002800174700002200202700001700224700002300241700002200264700002200286700001500308700001800323700001400341700002100355700002100376245012500397856006700522300001100589490000800600520143300608022001402041                                       d10amicrofluidic10aorgan on chip10apancreatic cancer10apatient derived organoids10aTumor Microenvironment1 aDarbaz Adnan1 aNatan Roberto de Barros1 aLuca S. Santovito1 aXuhong Cheng1 aKristi M. Lawrence1 aMariah K. Barnett1 aMartine D. Boetto1 aNeal Mehta1 aAjaypal Singh1 aLin Cheng1 aXiangsheng Huang1 aFaraz Bishehsari00aA Patient-Derived Organ-on-Chip Platform for Modeling the Tumor Microenvironment and Drug Responses in Pancreatic Cancer  uhttps://onlinelibrary.wiley.com/doi/abs/10.1002/advs.202508934  ae089340 vn/a3 aPancreatic 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.  a2198-3844