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Pancreatic Neoplasms: HELP
Articles by Ewan J. McGhee
Based on 9 articles published since 2010
(Why 9 articles?)
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Between 2010 and 2020, Ewan McGhee wrote the following 9 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article N-WASP Control of LPAR1 Trafficking Establishes Response to Self-Generated LPA Gradients to Promote Pancreatic Cancer Cell Metastasis. 2019

Juin, Amelie / Spence, Heather J / Martin, Kirsty J / McGhee, Ewan / Neilson, Matthew / Cutiongco, Marie F A / Gadegaard, Nikolaj / Mackay, Gillian / Fort, Loic / Lilla, Sergio / Kalna, Gabriela / Thomason, Peter / Koh, Yvette W H / Norman, Jim C / Insall, Robert H / Machesky, Laura M. ·CRUK Beatson Institute, Glasgow G61 1BD, UK. · Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow G12 8LT, UK. · CRUK Beatson Institute, Glasgow G61 1BD, UK; Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1BD, UK. · CRUK Beatson Institute, Glasgow G61 1BD, UK; Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1BD, UK. Electronic address: l.machesky@beatson.gla.ac.uk. ·Dev Cell · Pubmed #31668663.

ABSTRACT: Pancreatic ductal adenocarcinoma is one of the most invasive and metastatic cancers and has a dismal 5-year survival rate. We show that N-WASP drives pancreatic cancer metastasis, with roles in both chemotaxis and matrix remodeling. lysophosphatidic acid, a signaling lipid abundant in blood and ascites fluid, is both a mitogen and chemoattractant for cancer cells. Pancreatic cancer cells break lysophosphatidic acid down as they respond to it, setting up a self-generated gradient driving tumor egress. N-WASP-depleted cells do not recognize lysophosphatidic acid gradients, leading to altered RhoA activation, decreased contractility and traction forces, and reduced metastasis. We describe a signaling loop whereby N-WASP and the endocytic adapter SNX18 promote lysophosphatidic acid-induced RhoA-mediated contractility and force generation by controlling lysophosphatidic acid receptor recycling and preventing degradation. This chemotactic loop drives collagen remodeling, tumor invasion, and metastasis and could be an important target against pancreatic cancer spread.

2 Article CSF1R 2018

Candido, Juliana B / Morton, Jennifer P / Bailey, Peter / Campbell, Andrew D / Karim, Saadia A / Jamieson, Thomas / Lapienyte, Laura / Gopinathan, Aarthi / Clark, William / McGhee, Ewan J / Wang, Jun / Escorcio-Correia, Monica / Zollinger, Raphael / Roshani, Rozita / Drew, Lisa / Rishi, Loveena / Arkell, Rebecca / Evans, T R Jeffry / Nixon, Colin / Jodrell, Duncan I / Wilkinson, Robert W / Biankin, Andrew V / Barry, Simon T / Balkwill, Frances R / Sansom, Owen J. ·Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK. · Cancer Research UK Beatson Institute, Glasgow G61 1BD, UK; Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UK. · Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UK. · Cancer Research UK Beatson Institute, Glasgow G61 1BD, UK. · Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way, Cambridge CB2 0RE, UK. · Bioscience, Oncology, iMED Biotech Unit, AstraZeneca, Boston, MA, USA. · MedImmune Ltd, Granta Park, Cambridge CB21 6GH, UK. · Bioscience, Oncology, iMED Biotech Unit, AstraZeneca, Cambridge, UK. · Cancer Research UK Beatson Institute, Glasgow G61 1BD, UK; Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UK. Electronic address: o.sansom@beatson.gla.ac.uk. ·Cell Rep · Pubmed #29719257.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is resistant to most therapies including single-agent immunotherapy and has a dense desmoplastic stroma, and most patients present with advanced metastatic disease. We reveal that macrophages are the dominant leukocyte population both in human PDAC stroma and autochthonous models, with an important functional contribution to the squamous subtype of human PDAC. We targeted macrophages in a genetic PDAC model using AZD7507, a potent selective inhibitor of CSF1R. AZD7507 caused shrinkage of established tumors and increased mouse survival in this difficult-to-treat model. Malignant cell proliferation diminished, with increased cell death and an enhanced T cell immune response. Loss of macrophages rewired other features of the TME, with global changes in gene expression akin to switching PDAC subtypes. These changes were markedly different to those elicited when neutrophils were targeted via CXCR2. These results suggest targeting the myeloid cell axis may be particularly efficacious in PDAC, especially with CSF1R inhibitors.

3 Article A RhoA-FRET Biosensor Mouse for Intravital Imaging in Normal Tissue Homeostasis and Disease Contexts. 2017

Nobis, Max / Herrmann, David / Warren, Sean C / Kadir, Shereen / Leung, Wilfred / Killen, Monica / Magenau, Astrid / Stevenson, David / Lucas, Morghan C / Reischmann, Nadine / Vennin, Claire / Conway, James R W / Boulghourjian, Alice / Zaratzian, Anaiis / Law, Andrew M / Gallego-Ortega, David / Ormandy, Christopher J / Walters, Stacey N / Grey, Shane T / Bailey, Jacqueline / Chtanova, Tatyana / Quinn, Julian M W / Baldock, Paul A / Croucher, Peter I / Schwarz, Juliane P / Mrowinska, Agata / Zhang, Lei / Herzog, Herbert / Masedunskas, Andrius / Hardeman, Edna C / Gunning, Peter W / Del Monte-Nieto, Gonzalo / Harvey, Richard P / Samuel, Michael S / Pajic, Marina / McGhee, Ewan J / Johnsson, Anna-Karin E / Sansom, Owen J / Welch, Heidi C E / Morton, Jennifer P / Strathdee, Douglas / Anderson, Kurt I / Timpson, Paul. ·The Garvan Institute of Medical Research, St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia. · Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G611BD, UK. · Neuromuscular and Regenerative Medicine Unit, University of New South Wales, Sydney, NSW 2010, Australia; Oncology Research Unit, School of Medical Sciences, University of New South Wales, Sydney, NSW 2010, Australia. · Neuromuscular and Regenerative Medicine Unit, University of New South Wales, Sydney, NSW 2010, Australia. · Oncology Research Unit, School of Medical Sciences, University of New South Wales, Sydney, NSW 2010, Australia. · Developmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia; St. Vincent's Clinical School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia. · Centre for Cancer Biology, SA Pathology and University of South Australia School of Medicine, University of Adelaide, Adelaide, SA 5000, Australia. · Signalling Programme, Babraham Institute, Cambridge CB223AT, UK. · Francis Crick Institute, London NW11AT, UK. Electronic address: kurt.anderson@crick.ac.uk. · The Garvan Institute of Medical Research, St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia. Electronic address: p.timpson@garvan.org.au. ·Cell Rep · Pubmed #28978480.

ABSTRACT: The small GTPase RhoA is involved in a variety of fundamental processes in normal tissue. Spatiotemporal control of RhoA is thought to govern mechanosensing, growth, and motility of cells, while its deregulation is associated with disease development. Here, we describe the generation of a RhoA-fluorescence resonance energy transfer (FRET) biosensor mouse and its utility for monitoring real-time activity of RhoA in a variety of native tissues in vivo. We assess changes in RhoA activity during mechanosensing of osteocytes within the bone and during neutrophil migration. We also demonstrate spatiotemporal order of RhoA activity within crypt cells of the small intestine and during different stages of mammary gestation. Subsequently, we reveal co-option of RhoA activity in both invasive breast and pancreatic cancers, and we assess drug targeting in these disease settings, illustrating the potential for utilizing this mouse to study RhoA activity in vivo in real time.

4 Article Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy, and metastasis. 2017

Vennin, Claire / Chin, Venessa T / Warren, Sean C / Lucas, Morghan C / Herrmann, David / Magenau, Astrid / Melenec, Pauline / Walters, Stacey N / Del Monte-Nieto, Gonzalo / Conway, James R W / Nobis, Max / Allam, Amr H / McCloy, Rachael A / Currey, Nicola / Pinese, Mark / Boulghourjian, Alice / Zaratzian, Anaiis / Adam, Arne A S / Heu, Celine / Nagrial, Adnan M / Chou, Angela / Steinmann, Angela / Drury, Alison / Froio, Danielle / Giry-Laterriere, Marc / Harris, Nathanial L E / Phan, Tri / Jain, Rohit / Weninger, Wolfgang / McGhee, Ewan J / Whan, Renee / Johns, Amber L / Samra, Jaswinder S / Chantrill, Lorraine / Gill, Anthony J / Kohonen-Corish, Maija / Harvey, Richard P / Biankin, Andrew V / Anonymous3070902 / Evans, T R Jeffry / Anderson, Kurt I / Grey, Shane T / Ormandy, Christopher J / Gallego-Ortega, David / Wang, Yingxiao / Samuel, Michael S / Sansom, Owen J / Burgess, Andrew / Cox, Thomas R / Morton, Jennifer P / Pajic, Marina / Timpson, Paul. ·The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia. · St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia. · Developmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Sydney, New South Wales 2010, Australia. · Biomedical Imaging Facility, Mark Wainwright Analytical Centre, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales 2052, Australia. · Department of Pathology, St. Vincent's Hospital, Sydney, New South Wales 2010, Australia. · Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, New South Wales 2522, Australia. · Immune Imaging Program, Centenary Institute, University of Sydney, Sydney, New South Wales 2006, Australia. · University of Sydney Medical School, Sydney, New South Wales 2006, Australia. · Department of Dermatology, Royal Prince Alfred Hospital, Camperdown, New South Wales 2050, Australia. · Cancer Research UK Beatson Institute, Glasgow, Scotland G61 BD, U.K. · Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research and Royal North Shore Hospital, Sydney, New South Wales 2065, Australia. · University of Sydney, Sydney, New South Wales 2006, Australia. · Australian Pancreatic Cancer Genome Initiative. · Department of Surgery, Royal North Shore Hospital, Sydney, New South Wales 2065, Australia. · Macarthur Cancer Therapy Centre, Campbelltown Hospital, Sydney, New South Wales 2560, Australia. · School of Medicine, Western Sydney University, Penrith, Sydney, New South Wales 2751, Australia. · School of Biotechnology and Biomolecular Science, University of New South Wales, Sydney, New South Wales 2052, Australia. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Scotland G61 BD, U.K. · West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Scotland G61 BD, U.K. · Department of Bioengineering, Institute of Engineering in Medicine, University of California, San Diego, San Diego, CA 92121, USA. · Centre for Cancer Biology, SA Pathology and University of South Australia School of Medicine, University of Adelaide, Adelaide, South Australia 5000, Australia. · The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia. m.pajic@garvan.org.au p.timpson@garvan.org.au. ·Sci Transl Med · Pubmed #28381539.

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.

5 Article ROCK signaling promotes collagen remodeling to facilitate invasive pancreatic ductal adenocarcinoma tumor cell growth. 2017

Rath, Nicola / Morton, Jennifer P / Julian, Linda / Helbig, Lena / Kadir, Shereen / McGhee, Ewan J / Anderson, Kurt I / Kalna, Gabriela / Mullin, Margaret / Pinho, Andreia V / Rooman, Ilse / Samuel, Michael S / Olson, Michael F. ·Cancer Research UK Beatson Institute, Glasgow, UK. · Electron Microscopy Facility, School of Life Sciences, University of Glasgow, Glasgow, UK. · Cancer Research Program, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW, Australia. · Oncology Research Centre, Free University Brussels (VUB), Brussels, Belgium. · Centre for Cancer Biology, SA Pathology and the University of South Australia, Adelaide, SA, Australia. · Cancer Research UK Beatson Institute, Glasgow, UK m.olson@beatson.gla.ac.uk. · Institute of Cancer Sciences, University of Glasgow, Glasgow, UK. ·EMBO Mol Med · Pubmed #28031255.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer death; identifying PDAC enablers may reveal potential therapeutic targets. Expression of the actomyosin regulatory ROCK1 and ROCK2 kinases increased with tumor progression in human and mouse pancreatic tumors, while elevated ROCK1/ROCK2 expression in human patients, or conditional ROCK2 activation in a Kras

6 Article Intravital FRAP Imaging using an E-cadherin-GFP Mouse Reveals Disease- and Drug-Dependent Dynamic Regulation of Cell-Cell Junctions in Live Tissue. 2016

Erami, Zahra / Herrmann, David / Warren, Sean C / Nobis, Max / McGhee, Ewan J / Lucas, Morghan C / Leung, Wilfred / Reischmann, Nadine / Mrowinska, Agata / Schwarz, Juliane P / Kadir, Shereen / Conway, James R W / Vennin, Claire / Karim, Saadia A / Campbell, Andrew D / Gallego-Ortega, David / Magenau, Astrid / Murphy, Kendelle J / Ridgway, Rachel A / Law, Andrew M / Walters, Stacey N / Grey, Shane T / Croucher, David R / Zhang, Lei / Herzog, Herbert / Hardeman, Edna C / Gunning, Peter W / Ormandy, Christopher J / Evans, T R Jeffry / Strathdee, Douglas / Sansom, Owen J / Morton, Jennifer P / Anderson, Kurt I / Timpson, Paul. ·Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK. · The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia. · Neuromuscular and Regenerative Medicine Unit, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia. · Oncology Research Unit, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia. · Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK. Electronic address: k.anderson@beatson.gla.ac.uk. · The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia. Electronic address: p.timpson@garvan.org.au. ·Cell Rep · Pubmed #26725115.

ABSTRACT: E-cadherin-mediated cell-cell junctions play a prominent role in maintaining the epithelial architecture. The disruption or deregulation of these adhesions in cancer can lead to the collapse of tumor epithelia that precedes invasion and subsequent metastasis. Here we generated an E-cadherin-GFP mouse that enables intravital photobleaching and quantification of E-cadherin mobility in live tissue without affecting normal biology. We demonstrate the broad applications of this mouse by examining E-cadherin regulation in multiple tissues, including mammary, brain, liver, and kidney tissue, while specifically monitoring E-cadherin mobility during disease progression in the pancreas. We assess E-cadherin stability in native pancreatic tissue upon genetic manipulation involving Kras and p53 or in response to anti-invasive drug treatment and gain insights into the dynamic remodeling of E-cadherin during in situ cancer progression. FRAP in the E-cadherin-GFP mouse, therefore, promises to be a valuable tool to fundamentally expand our understanding of E-cadherin-mediated events in native microenvironments.

7 Article Targeting the LOX/hypoxia axis reverses many of the features that make pancreatic cancer deadly: inhibition of LOX abrogates metastasis and enhances drug efficacy. 2015

Miller, Bryan W / Morton, Jennifer P / Pinese, Mark / Saturno, Grazia / Jamieson, Nigel B / McGhee, Ewan / Timpson, Paul / Leach, Joshua / McGarry, Lynn / Shanks, Emma / Bailey, Peter / Chang, David / Oien, Karin / Karim, Saadia / Au, Amy / Steele, Colin / Carter, Christopher Ross / McKay, Colin / Anderson, Kurt / Evans, Thomas R Jeffry / Marais, Richard / Springer, Caroline / Biankin, Andrew / Erler, Janine T / Sansom, Owen J. ·Cancer Research UK Beatson Institute Garscube Estate, Glasgow, UK. · The Garvan Institute of Medical Research, Sydney, NSW, Australia. · Cancer Research UK Manchester Institute, Withington Manchester, UK. · West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK. · Institute of Cancer Sciences University of Glasgow Garscube Estate, Glasgow, UK. · Cancer Research UK Beatson Institute Garscube Estate, Glasgow, UK Institute of Cancer Sciences University of Glasgow Garscube Estate, Glasgow, UK. · Institute of Cancer Research, London, UK. · Biotech Research & Innovation Centre (BRIC), University of Copenhagen, Copenhagen (UCPH), Denmark janine.erler@bric.ku.dk o.sansom@beatson.gla.ac.uk. · Cancer Research UK Beatson Institute Garscube Estate, Glasgow, UK janine.erler@bric.ku.dk o.sansom@beatson.gla.ac.uk. ·EMBO Mol Med · Pubmed #26077591.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related mortality. Despite significant advances made in the treatment of other cancers, current chemotherapies offer little survival benefit in this disease. Pancreaticoduodenectomy offers patients the possibility of a cure, but most will die of recurrent or metastatic disease. Hence, preventing metastatic disease in these patients would be of significant benefit. Using principal component analysis (PCA), we identified a LOX/hypoxia signature associated with poor patient survival in resectable patients. We found that LOX expression is upregulated in metastatic tumors from Pdx1-Cre Kras(G12D/+) Trp53(R172H/+) (KPC) mice and that inhibition of LOX in these mice suppressed metastasis. Mechanistically, LOX inhibition suppressed both migration and invasion of KPC cells. LOX inhibition also synergized with gemcitabine to kill tumors and significantly prolonged tumor-free survival in KPC mice with early-stage tumors. This was associated with stromal alterations, including increased vasculature and decreased fibrillar collagen, and increased infiltration of macrophages and neutrophils into tumors. Therefore, LOX inhibition is able to reverse many of the features that make PDAC inherently refractory to conventional therapies and targeting LOX could improve outcome in surgically resectable disease.

8 Article Intravital FLIM-FRET imaging reveals dasatinib-induced spatial control of src in pancreatic cancer. 2013

Nobis, Max / McGhee, Ewan J / Morton, Jennifer P / Schwarz, Juliane P / Karim, Saadia A / Quinn, Jean / Edward, Mike / Campbell, Andrew D / McGarry, Lynn C / Evans, T R Jeffry / Brunton, Valerie G / Frame, Margaret C / Carragher, Neil O / Wang, Yingxiao / Sansom, Owen J / Timpson, Paul / Anderson, Kurt I. ·The Beatson Institute for Cancer Research, Glasgow; Section of Dermatology, School of Medicine, University of Glasgow, Glasgow, UK. ·Cancer Res · Pubmed #23749641.

ABSTRACT: Cancer invasion and metastasis occur in a complex three-dimensional (3D) environment, with reciprocal feedback from the surrounding host tissue and vasculature-governing behavior. In this study, we used a novel intravital method that revealed spatiotemporal regulation of Src activity in response to the anti-invasive Src inhibitor dasatinib. A fluorescence lifetime imaging microscopy-fluorescence resonance energy transfer (FLIM-FRET) Src biosensor was used to monitor drug-targeting efficacy in a transgenic p53-mutant mouse model of pancreatic cancer. In contrast to conventional techniques, FLIM-FRET analysis allowed for accurate, time-dependent, live monitoring of drug efficacy and clearance in live tumors. In 3D organotypic cultures, we showed that a spatially distinct gradient of Src activity exists within invading tumor cells, governed by the depth of penetration into complex matrices. In parallel, this gradient was also found to exist within live tumors, where Src activity is enhanced at the invasive border relative to the tumor cortex. Upon treatment with dasatinib, we observed a switch in activity at the invasive borders, correlating with impaired metastatic capacity in vivo. Src regulation was governed by the proximity of cells to the host vasculature, as cells distal to the vasculature were regulated differentially in response to drug treatment compared with cells proximal to the vasculature. Overall, our results in live tumors revealed that a threshold of drug penetrance exists in vivo and that this can be used to map areas of poor drug-targeting efficiency within specific tumor microenvironments. We propose that using FLIM-FRET in this capacity could provide a useful preclinical tool in animal models before clinical translation.

9 Article Spatial regulation of RhoA activity during pancreatic cancer cell invasion driven by mutant p53. 2011

Timpson, Paul / McGhee, Ewan J / Morton, Jennifer P / von Kriegsheim, Alex / Schwarz, Juliane P / Karim, Saadia A / Doyle, Brendan / Quinn, Jean A / Carragher, Neil O / Edward, Mike / Olson, Michael F / Frame, Margaret C / Brunton, Valerie G / Sansom, Owen J / Anderson, Kurt I. ·The Beatson Institute for Cancer Research, Garscube Estate, Glasgow, United Kingdom. p.timpson@beatson.gla.ac.uk ·Cancer Res · Pubmed #21266354.

ABSTRACT: The ability to observe changes in molecular behavior during cancer cell invasion in vivo remains a major challenge to our understanding of the metastatic process. Here, we demonstrate for the first time, an analysis of RhoA activity at a subcellular level using FLIM-FRET (fluorescence lifetime imaging microscopy-fluorescence resonance energy transfer) imaging in a live animal model of pancreatic cancer. In invasive mouse pancreatic ductal adenocarcinoma (PDAC) cells driven by mutant p53 (p53(R172H)), we observed a discrete fraction of high RhoA activity at both the leading edge and rear of cells in vivo which was absent in two-dimensional in vitro cultures. Notably, this pool of active RhoA was absent in noninvasive p53(fl) knockout PDAC cells, correlating with their poor invasive potential in vivo. We used dasatanib, a clinically approved anti-invasive agent that is active in this model, to illustrate the functional importance of spatially regulated RhoA. Dasatanib inhibited the activity of RhoA at the poles of p53(R172H) cells in vivo and this effect was independent of basal RhoA activity within the cell body. Taken together, quantitative in vivo fluorescence lifetime imaging illustrated that RhoA is not only necessary for invasion, but also that subcellular spatial regulation of RhoA activity, as opposed to its global activity, is likely to govern invasion efficiency in vivo. Our findings reveal the utility of FLIM-FRET in analyzing dynamic biomarkers during drug treatment in living animals, and they also show how discrete intracellular molecular pools might be differentially manipulated by future anti-invasive therapies.