Intravital imaging technology guides FAK-mediated priming in pancreatic cancer precision medicine according to Merlin status - Archive ouverte HAL
Article Dans Une Revue Science Advances Année : 2021

Intravital imaging technology guides FAK-mediated priming in pancreatic cancer precision medicine according to Merlin status

Résumé

Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic, chemoresistant malignancy and is characterized by a dense, desmoplastic stroma that modulates PDAC progression. Here, we visualized transient manipulation of focal adhesion kinase (FAK), which integrates bidirectional cell-environment signaling, using intravital fluorescence lifetime imaging microscopy of the FAK-based Förster resonance energy transfer biosensor in mouse and patient-derived PDAC models. Parallel real-time quantification of the FUCCI cell cycle reporter guided us to improve PDAC response to standard-of-care chemotherapy at primary and secondary sites. Critically, micropatterned pillar plates and stiffness-tunable matrices were used to pinpoint the contribution of environmental cues to chemosensitization, while fluid flow–induced shear stress assessment, patient-derived matrices, and personalized in vivo models allowed us to deconstruct how FAK inhibition can reduce PDAC spread. Last, stratification of PDAC patient samples via Merlin status revealed a patient subset with poor prognosis that are likely to respond to FAK priming before chemotherapy.
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Dates et versions

hal-03957015 , version 1 (25-01-2023)

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Kendelle J. Murphy, Daniel A. Reed, Claire Vennin, James R. W. Conway, Max Nobis, et al.. Intravital imaging technology guides FAK-mediated priming in pancreatic cancer precision medicine according to Merlin status. Science Advances , 2021, 7 (40), ⟨10.1126/sciadv.abh0363⟩. ⟨hal-03957015⟩

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