OBJECTIVE: To investigate the feasibility of using implantable microdevices (IMDs) in pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy with limited treatment options. IMDs permit localized delivery of multiple therapies with simultaneous in vivo assessment of tumor response. Although IMDs have previously been evaluated in multiple malignancies, their application in PDAC has not been reported. METHODS: Xenograft tumors were generated by injecting PDAC patient-derived organoids (PDO) into mouse pancreata. IMDs loaded with standard-of-care chemotherapeutic drugs including gemcitabine, paclitaxel, SN38 (irinotecan metabolite), oxaliplatin, and 5-fluorouracil were then inserted into the tumor during laparotomy. Mice were sacrificed at 4 or 24 hours after insertion. Immunofluorescence was performed to assess biomarkers of DNA damage (γH2AX), apoptosis (cleaved caspase-3; CC3), and proliferation (Ki67). RESULTS: Fourteen mice underwent IMD placement with successful device retrieval and analysis. CC3 and γH2AX analyses revealed treatment specific biologic response, with the most pronounced response at 24 hours. Ki67 analysis demonstrated reduction of the proliferation within treated regions at both 4 and 24 hours compared to controls. Overall, the IMD enabled localized chemotherapy delivery and concurrent assessment of responses to multiple chemotherapeutic agents in an in vivo setting. CONCLUSION: Intra-pancreatic IMD deployment in orthotopic PDAC organoid tumors presents a feasible approach to assess chemotherapy sensitivities. Changes in proliferation revealed drug specific response at all timepoints, while apoptotic markers required longer incubation. These data support further investigation into the intra-operative or endoscopic deployment of IMDs as a platform for precision medicine.
Standring et al. (Mon,) studied this question.