Vennin, Claire and Chin, Venessa T and Warren, Sean C and Lucas, Morghan C and Herrmann, David and Magenau, Astrid and Melenec, Pauline and Walters, Stacey N and Del Monte-Nieto, Gonzalo and Conway, James R W and Nobis, Max and Allam, Amr H and McCloy, Rachael A and Currey, Nicola and Pinese, Mark and Boulghourjian, Alice and Zaratzian, Anaiis and Adam, Arne A S and Heu, Celine and Nagrial, Adnan M and Chou, Angela and Steinmann, Angela and Drury, Alison and Froio, Danielle and Giry-Laterriere, Marc and Harris, Nathanial L E and Phan, Tri and Jain, Rohit and Weninger, Wolfgang and McGhee, Ewan J and Whan, Renee and Johns, Amber L and Samra, Jaswinder S and Chantrill, Lorraine and Gill, Anthony J and Kohonen-Corish, Maija and Harvey, Richard P and Biankin, Andrew V and Evans, T R Jeffry and Anderson, Kurt I and Grey, Shane T and Ormandy, Christopher J and Gallego-Ortega, David and Wang, Yingxiao and Samuel, Michael S and Sansom, Owen J and Burgess, Andrew and Cox, Thomas R and Morton, Jennifer P and Pajic, Marina and Timpson, Paul (2017) Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy, and metastasis. Science Translational Medicine, 9 (384). pp. eaai8504. ISSN 1946-6242 (Not OA)
Full text not available from this repository.Abstract
The emerging standard of care for patients with inoperable pancreatic cancer is a combination of cytotoxic drugs gemcitabine and Abraxane, but patient response remains moderate. Pancreatic cancer development and metastasis occur in complex settings, with reciprocal feedback from microenvironmental cues influencing both disease progression and drug response. Little is known about how sequential dual targeting of tumor tissue tension and vasculature before chemotherapy can affect tumor response. We used intravital imaging to assess how transient manipulation of the tumor tissue, or "priming," using the pharmaceutical Rho kinase inhibitor Fasudil affects response to chemotherapy. Intravital Förster resonance energy transfer imaging of a cyclin-dependent kinase 1 biosensor to monitor the efficacy of cytotoxic drugs revealed that priming improves pancreatic cancer response to gemcitabine/Abraxane at both primary and secondary sites. Transient priming also sensitized cells to shear stress and impaired colonization efficiency and fibrotic niche remodeling within the liver, three important features of cancer spread. Last, we demonstrate a graded response to priming in stratified patient-derived tumors, indicating that fine-tuned tissue manipulation before chemotherapy may offer opportunities in both primary and metastatic targeting of pancreatic cancer.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 11 Apr 2017 01:45 |
| Last Modified: | 29 Jan 2018 00:15 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/581 |
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