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

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

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1126/sciadv.abh0363
Journal or Publication Title: Science Advances
Volume: 7
Number: 40
Date: October 2021
Divisions: Immune Imaging
Depositing User: General Admin
Identification Number: 10.1126/sciadv.abh0363
ISSN: 2375-2548
Date Deposited: 05 Dec 2021 05:54
Abstract:

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.

Creators:
Creators
Email
Murphy, Kendelle J.
UNSPECIFIED
Reed, Daniel A.
UNSPECIFIED
Vennin, Claire
UNSPECIFIED
Conway, James R. W.
UNSPECIFIED
Nobis, Max
UNSPECIFIED
Yin, Julia X.
UNSPECIFIED
Chambers, Cecilia R.
UNSPECIFIED
Pereira, Brooke A.
UNSPECIFIED
Lee, Victoria
UNSPECIFIED
Filipe, Elysse C.
UNSPECIFIED
Trpceski, Michael
UNSPECIFIED
Ritchie, Shona
UNSPECIFIED
Lucas, Morghan C.
UNSPECIFIED
Warren, Sean C.
UNSPECIFIED
Skhinas, Joanna N.
UNSPECIFIED
Magenau, Astrid
UNSPECIFIED
Metcalf, Xanthe L.
UNSPECIFIED
Stoehr, Janett
UNSPECIFIED
Major, Gretel
UNSPECIFIED
Parkin, Ashleigh
UNSPECIFIED
Bidanel, Romain
UNSPECIFIED
Lyons, Ruth J.
UNSPECIFIED
Zaratzian, Anaiis
UNSPECIFIED
Tayao, Michael
UNSPECIFIED
Da Silva, Andrew
UNSPECIFIED
Abdulkhalek, Lea
UNSPECIFIED
Gill, Anthony J.
UNSPECIFIED
Johns, Amber L.
UNSPECIFIED
Biankin, Andrew V.
UNSPECIFIED
Samra, Jaswinder
UNSPECIFIED
Grimmond, Sean M.
UNSPECIFIED
Chou, Angela
UNSPECIFIED
Goetz, Jacky G.
UNSPECIFIED
Samuel, Michael S.
UNSPECIFIED
Lyons, J. Guy
UNSPECIFIED
Burgess, Andrew
UNSPECIFIED
Caldon, C. Elizabeth
UNSPECIFIED
Horvath, Lisa G.
UNSPECIFIED
Daly, Roger J.
UNSPECIFIED
Gadegaard, Nikolaj
UNSPECIFIED
Wang, Yingxiao
UNSPECIFIED
Sansom, Owen J.
UNSPECIFIED
Morton, Jennifer P.
UNSPECIFIED
Cox, Thomas R.
UNSPECIFIED
Pajic, Marina
UNSPECIFIED
Herrmann, David
UNSPECIFIED
Timpson, Paul
UNSPECIFIED
Last Modified: 06 Dec 2021 03:33
URI: https://eprints.centenary.org.au/id/eprint/1182

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