ArticleScience translational medicine2017
Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy, and metastasis.
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Article in Science translational medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers.
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155citing papers in PubMed
13.7field-weighted citation impact, top 1% of its field
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Who cites it
155 citing papers in PubMed, 264 citations in OpenAlex.
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- Nanotension Relief Agent Enhances Tissue Penetration by Reducing Solid Stress in Pancreatic Ductal Adenocarcinoma via Rho/ROCK Pathway Inhibition.Biomaterials research · 2025Article
- Rho/ROCK Pathway as a Therapeutic Target in Multiple Diseases.International journal of drug discovery and pharmacology · 2025Article
- Unveiling the resistance to therapies in pancreatic ductal adenocarcinoma.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024Review
95 more citing papers are in PubMed but not listed here.
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Authors and funding
52 authors at 10 institutions in 3 countries.
Claire VenninThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
Venessa T ChinThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.ORCID 0000-0002-4630-4451
Sean C WarrenThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.ORCID 0000-0002-5253-7147
Morghan C LucasThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.ORCID 0000-0001-7654-9137
David HerrmannThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.ORCID 0000-0002-9514-7501
Astrid MagenauThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
Pauline MelenecThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.ORCID 0000-0001-6486-2003
Stacey N WaltersThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.ORCID 0000-0001-5937-2341
Gonzalo Del Monte-NietoSt. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia.ORCID 0000-0003-3830-2226
James R W ConwayThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
Max NobisThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.ORCID 0000-0002-1861-1390
Amr H AllamThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
Rachael A McCloyThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.ORCID 0000-0001-7791-4044
Nicola CurreyThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
Mark PineseThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.ORCID 0000-0001-5078-6687
Alice BoulghourjianThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
Anaiis ZaratzianThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
Arne A S AdamDevelopmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Sydney, New South Wales 2010, Australia.
Celine HeuBiomedical Imaging Facility, Mark Wainwright Analytical Centre, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales 2052, Australia.
Adnan M NagrialThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
Angela ChouThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
Angela SteinmannThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
Alison DruryThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.ORCID 0000-0002-4858-0724
Danielle FroioThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.ORCID 0000-0001-9043-8935
Marc Giry-LaterriereThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.ORCID 0000-0001-9043-8935
Nathanial L E HarrisThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
Tri PhanThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.ORCID 0000-0002-4909-2984
Rohit JainImmune Imaging Program, Centenary Institute, University of Sydney, Sydney, New South Wales 2006, Australia.
Wolfgang WeningerImmune Imaging Program, Centenary Institute, University of Sydney, Sydney, New South Wales 2006, Australia.
Ewan J McGheeCancer Research UK Beatson Institute, Glasgow, Scotland G61 BD, U.K.
Renee WhanDevelopmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Sydney, New South Wales 2010, Australia.ORCID 0000-0002-6664-6344
Amber L JohnsThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
Jaswinder S SamraCancer Research UK Beatson Institute, Glasgow, Scotland G61 BD, U.K.
Lorraine ChantrillThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
Anthony J GillThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.ORCID 0000-0002-9447-1967
Maija Kohonen-CorishThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
Richard P HarveySt. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia.
Andrew V BiankinAustralian Pancreatic Cancer Genome Initiative.ORCID 0000-0002-0362-5597
Australian Pancreatic Cancer Genome Initiative (APGI)
T R Jeffry EvansCancer Research UK Beatson Institute, Glasgow, Scotland G61 BD, U.K.
Kurt I AndersonCancer Research UK Beatson Institute, Glasgow, Scotland G61 BD, U.K.
Shane T GreyThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
Christopher J OrmandyThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.ORCID 0000-0002-2504-7919
David Gallego-OrtegaThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.ORCID 0000-0002-2347-7835
Yingxiao WangDepartment of Bioengineering, Institute of Engineering in Medicine, University of California, San Diego, San Diego, CA 92121, USA.
Michael S SamuelCentre for Cancer Biology, SA Pathology and University of South Australia School of Medicine, University of Adelaide, Adelaide, South Australia 5000, Australia.ORCID 0000-0001-7880-6379
Owen J SansomCancer Research UK Beatson Institute, Glasgow, Scotland G61 BD, U.K.
Andrew BurgessThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.ORCID 0000-0003-4536-9226
Thomas R CoxThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.ORCID 0000-0001-9294-1745
Jennifer P MortonCancer Research UK Beatson Institute, Glasgow, Scotland G61 BD, U.K.ORCID 0000-0001-5766-9141
Marina PajicThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia. m.pajic@garvan.org.au p.timpson@garvan.org.au.
Paul TimpsonThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia. m.pajic@garvan.org.au p.timpson@garvan.org.au.
Garvan Institute of Medical Research · AUVictor Chang Cardiac Research Institute · AUCancer Research UK Scotland Institute · GBThe University of Sydney · AUBeatson West of Scotland Cancer Centre · GBCamden and Campbelltown Hospitals · AUCentre for Cancer Biology · AURoyal North Shore Hospital · AUUniversity of San Diego · USUNSW Sydney · AU
Funding
Role of Spatiotemporal Epigenetic Dynamics in Regulating Endothelial Gene Expressions under FlowsR01HL121365 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CHIEN, SHU, WANG, YINGXIAO · 2014 to 2025
$7.5MLocus-specific Imaging of Dynamic Histone Methylations during ReprogrammingR01GM125379 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHIEN, SHU, WANG, YINGXIAO · 2017 to 2020
$2.4MMultiplex FRET Imaging of Kinase-Epigenome Interregulations in Live Cancer CellsR33CA204704 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WANG, YINGXIAO · 2017 to 2019
$1.1MThe Integration of FLIM and FRET for the Visualization of Flow-induced MolecularK02HL109142 · NHLBI · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI WANG, YINGXIAO · 2011 to 2015
$549kCancer Research UK 11650Cancer Research UK 12946Cancer Research UK 15565Cancer Research UK 20409Cancer Research UK 21139Cancer Research UK 22533Medical Research Council MR/N005813/1NCI NIH HHS R33 CA204704NHLBI NIH HHS K02 HL109142NHLBI NIH HHS R01 HL121365NIGMS NIH HHS R01 GM125379
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.
Indexed as
Disease Progression1-(5-Isoquinolinesulfonyl)-2-MethylpiperazineActin CytoskeletonAlbumin-Bound PaclitaxelAnimalsAntineoplastic AgentsBiosensing TechniquesCDC2 Protein KinaseCell Line, TumorCell ProliferationCollagenDeoxycytidineExtracellular MatrixGemcitabineHumansLiver1-(5-Isoquinolinesulfonyl)-2-MethylpiperazineAlbumin-Bound PaclitaxelAntineoplastic AgentsCDC2 Protein KinaseCDK1 protein, humanCollagenDeoxycytidinefasudilGemcitabineProtein Kinase Inhibitorsrho-Associated Kinasessrc-Family Kinases
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.