Tesson, Mathias and Stevenson, Katrina and Karim, Saadia A. and Nixon, Colin and Chalmers, Anthony J. and Sansom, Owen J. and O'Neill, Eric and Jones, Keaton and Morton, Jennifer P. (2024) Targeted irradiation in an autochthonous mouse model of pancreatic cancer. Disease Models and Mechanisms, 17 (3): dmm050463. ISSN 1754-8403

Abstract

The value of radiotherapy in the treatment of pancreatic cancer has been the subject of much debate but limited preclinical research. We hypothesise that the poor translation of radiation research into clinical trials of radiotherapy in pancreatic cancer is due, in part, to inadequate preclinical study models. Here, we have developed and refined methods for targeted irradiation in autochthonous mouse models of pancreatic cancer, using a small animal radiotherapy research platform. We tested and optimised strategies for administration of contrast agents, iohexol and the liver imaging agent Fenestra LC, to enable the use of computed tomography imaging in tumour localisation. We demonstrate accurate tumour-targeting, negligible off-target effects, and therapeutic efficacy, depending on dose, number of fractions and tumour size, and provide proof-of-concept that precise radiation can be delivered effectively to mouse pancreatic tumours with a clinically relevant microenvironment. This advance will allow investigation of the radiation response in murine pancreatic cancer, discovery of mechanisms and biomarkers of radiosensitivity or resistance, and development of radiosensitising strategies to inform clinical trials for precision radiotherapy in this disease.

People
Tesson, Mathias
Author

Tesson, Mathias and Stevenson, Katrina and Karim, Saadia A. and Nixon, Colin and Chalmers, Anthony J. and Sansom, Owen J. and O'Neill, Eric and Jones, Keaton and Morton, Jennifer P. (2024) Targeted irradiation in an autochthonous mouse model of pancreatic cancer. Disease Models and Mechanisms, 17 (3): dmm050463. ISSN 1754-8403

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Stevenson, Katrina
Author

Tesson, Mathias and Stevenson, Katrina and Karim, Saadia A. and Nixon, Colin and Chalmers, Anthony J. and Sansom, Owen J. and O'Neill, Eric and Jones, Keaton and Morton, Jennifer P. (2024) Targeted irradiation in an autochthonous mouse model of pancreatic cancer. Disease Models and Mechanisms, 17 (3): dmm050463. ISSN 1754-8403

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Karim, Saadia A.
Author

Tesson, Mathias and Stevenson, Katrina and Karim, Saadia A. and Nixon, Colin and Chalmers, Anthony J. and Sansom, Owen J. and O'Neill, Eric and Jones, Keaton and Morton, Jennifer P. (2024) Targeted irradiation in an autochthonous mouse model of pancreatic cancer. Disease Models and Mechanisms, 17 (3): dmm050463. ISSN 1754-8403

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Nixon, Colin
Author

Tesson, Mathias and Stevenson, Katrina and Karim, Saadia A. and Nixon, Colin and Chalmers, Anthony J. and Sansom, Owen J. and O'Neill, Eric and Jones, Keaton and Morton, Jennifer P. (2024) Targeted irradiation in an autochthonous mouse model of pancreatic cancer. Disease Models and Mechanisms, 17 (3): dmm050463. ISSN 1754-8403

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Chalmers, Anthony
Author

Williamson, Aoife and Houston, Peter and Paterson, Jennifer and Chalmers, Anthony J. and McLoone, Philip and Fullerton, Natasha and Foo, Sin Yee and James, Allan and Nowicki, Stefan (2024) Dosimetric comparison of hippocampal sparing technologies in patients with low grade glioma. Neuro-Oncology Advances, 6 (1): vdae131. ISSN 2632-2498

Jackson, Mark R. and Richards, Amanda R. and Oladipupo, Abdul-Basit Ayoola and Chahal, Sandeep K. and Caragher, Seamus and Chalmers, Anthony J. and Gomez-Roman, Natividad (2024) ClonoScreen3D - a novel three-dimensional clonogenic screening platform for identification of radiosensitizers for glioblastoma. International Journal of Radiation Oncology, Biology, Physics, 120 (1). pp. 162-177. ISSN 0360-3016

Boele, Florien and Rosenlund, Lena and Nordentoft, Sara and Melhuish, Sara and Nicklin, Emma and Rydén, Isabelle and Williamson, Aoife and Donders-Kamphuis, Marike and Preusser, Matthias and Le Rhun, Emilie and Kiesel, Barbara and Minniti, Giuseppe and Furtner, Julia and Dirven, Linda and Taphoorn, Martin and Galldiks, Norbert and Rudà, Roberta and Chalmers, Anthony and Short, Susan C. and Piil, Karin and the Nurse and Allied Health Professionals Committee and the Disparity and Inclusion Committee of EANO (2024) Inequalities in access to neuro-oncology supportive care and rehabilitation: a survey of healthcare professionals’ perspectives. Neuro-Oncology Practice, 11 (4). pp. 484-493. ISSN 2054-2577

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Sansom, Owen
Author

Lu, Yuting and Travnickova, Jana and Badonyi, Mihaly and Rambow, Florian and Coates, Andrea and Khan, Zaid and Marques, Jair and Murphy, Laura C. and Garcia-Martinez, Pablo and Marais, Richard and Louphrasitthiphol, Pakavarin and Chan, Alex H.Y. and Schofield, Christopher J. and von Kriegsheim, Alex and Marsh, Joseph A. and Pavet, Valeria and Sansom, Owen J. and Illingworth, Robert S. and Patton, E. Elizabeth (2024) ALDH1A3-acetaldehyde metabolism potentiates transcriptional heterogeneity in melanoma. Cell Reports, 43 (7): 114406. ISSN 2639-1856

Pereira, Brooke A. and Ritchie, Shona and Chambers, Cecilia R. and Gordon, Katie A. and Magenau, Astrid and Murphy, Kendelle J. and Nobis, Max and Tyma, Victoria M. and Liew, Ying Fei and Lucas, Morghan C. and Naeini, Marjan M. and Barkauskas, Deborah S. and Chacon-Fajardo, Diego and Howell, Anna E. and Parker, Amelia L. and Warren, Sean C. and Reed, Daniel A. and Lee, Victoria and Metcalf, Xanthe L. and Lee, Young Kyung and O'Regan, Luke P. and Zhu, Jessie and Trpceski, Michael and Fontaine, Angela R.M. and Stoehr, Janett and Rouet, Romain and Lin, Xufeng and Chitty, Jessica L. and Porazinski, Sean and Wu, Sunny Z. and Filipe, Elysse C. and Cadell, Antonia L. and Holliday, Holly and Yang, Jessica and Papanicolaou, Michael and Lyons, Ruth J. and Zaratzian, Anaiis and Tayao, Michael and Da Silva, Andrew and Vennin, Claire and Yin, Julia and Dew, Alysha B. and McMillan, Paul J. and Goldstein, Leonard D. and Deveson, Ira W. and Croucher, David R. and Samuel, Michael S. and Sim, Hao-Wen and Batten, Marcel and Chantrill, Lorraine and Grimmond, Sean M. and Gill, Anthony J. and Samra, Jaswinder and Evans, Thomas R. Jeffry and Sasaki, Takako and Phan, Tri G. and Swarbrick, Alexander and Sansom, Owen J. and Morton, Jennifer P. and Australian Pancreatic Cancer Matrix Atlas (APMA) and Australian Pancreatic Cancer Genome Initiative (APGI) and Pajic, Marina and Parker, Benjamin L. and Herrmann, David and Cox, Thomas R. and Timpson, Paul (2024) Temporally resolved proteomics identifies nidogen-2 as a cotarget in pancreatic cancer that modulates fibrosis and therapy response. Science Advances, 10 (27): eadl1197. ISSN 2375-2548

Malla, Sudhir B. and Byrne, Ryan M. and Lafarge, Maxime W. and Corry, Shania M. and Fisher, Natalie C. and Tsantoulis, Petros K. and Mills, Megan L. and Ridgway, Rachel A. and Lannagan, Tamsin R. M. and Najumudeen, Arafath K. and Gilroy, Kathryn L. and Amirkhah, Raheleh and Maguire, Sarah L. and Mulholland, Eoghan J. and Belnoue-Davis, Hayley L. and Grassi, Elena and Viviani, Marco and Rogan, Emily and Redmond, Keara L. and Sakhnevych, Svetlana and McCooey, Aoife J. and Bull, Courtney and Hoey, Emily and Sinevici, Nicoleta and Hall, Holly and Ahmaderaghi, Baharak and Domingo, Enric and Blake, Andrew and Richman, Susan D. and Isella, Claudio and Miller, Crispin and Bertotti, Andrea and Trusolino, Livio and Loughrey, Maurice B. and Kerr, Emma M. and Tejpar, Sabine and S:CORT Consortium and Maughan, Timothy S. and Lawler, Mark and Campbell, Andrew D. and Leedham, Simon J. and Koelzer, Viktor H. and Sansom, Owen J. and Dunne, Philip D. (2024) Author Correction: Pathway level subtyping identifies a slow-cycling biological phenotype associated with poor clinical outcomes in colorectal cancer. Nature Genetics, 56 (6): 1321. ISSN 1061-4036

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O'Neill, Eric
Author

Tesson, Mathias and Stevenson, Katrina and Karim, Saadia A. and Nixon, Colin and Chalmers, Anthony J. and Sansom, Owen J. and O'Neill, Eric and Jones, Keaton and Morton, Jennifer P. (2024) Targeted irradiation in an autochthonous mouse model of pancreatic cancer. Disease Models and Mechanisms, 17 (3): dmm050463. ISSN 1754-8403

See full publications list
Jones, Keaton
Author

Tesson, Mathias and Stevenson, Katrina and Karim, Saadia A. and Nixon, Colin and Chalmers, Anthony J. and Sansom, Owen J. and O'Neill, Eric and Jones, Keaton and Morton, Jennifer P. (2024) Targeted irradiation in an autochthonous mouse model of pancreatic cancer. Disease Models and Mechanisms, 17 (3): dmm050463. ISSN 1754-8403

See full publications list
Morton, Jennifer P.
Author

Pereira, Brooke A. and Ritchie, Shona and Chambers, Cecilia R. and Gordon, Katie A. and Magenau, Astrid and Murphy, Kendelle J. and Nobis, Max and Tyma, Victoria M. and Liew, Ying Fei and Lucas, Morghan C. and Naeini, Marjan M. and Barkauskas, Deborah S. and Chacon-Fajardo, Diego and Howell, Anna E. and Parker, Amelia L. and Warren, Sean C. and Reed, Daniel A. and Lee, Victoria and Metcalf, Xanthe L. and Lee, Young Kyung and O'Regan, Luke P. and Zhu, Jessie and Trpceski, Michael and Fontaine, Angela R.M. and Stoehr, Janett and Rouet, Romain and Lin, Xufeng and Chitty, Jessica L. and Porazinski, Sean and Wu, Sunny Z. and Filipe, Elysse C. and Cadell, Antonia L. and Holliday, Holly and Yang, Jessica and Papanicolaou, Michael and Lyons, Ruth J. and Zaratzian, Anaiis and Tayao, Michael and Da Silva, Andrew and Vennin, Claire and Yin, Julia and Dew, Alysha B. and McMillan, Paul J. and Goldstein, Leonard D. and Deveson, Ira W. and Croucher, David R. and Samuel, Michael S. and Sim, Hao-Wen and Batten, Marcel and Chantrill, Lorraine and Grimmond, Sean M. and Gill, Anthony J. and Samra, Jaswinder and Evans, Thomas R. Jeffry and Sasaki, Takako and Phan, Tri G. and Swarbrick, Alexander and Sansom, Owen J. and Morton, Jennifer P. and Australian Pancreatic Cancer Matrix Atlas (APMA) and Australian Pancreatic Cancer Genome Initiative (APGI) and Pajic, Marina and Parker, Benjamin L. and Herrmann, David and Cox, Thomas R. and Timpson, Paul (2024) Temporally resolved proteomics identifies nidogen-2 as a cotarget in pancreatic cancer that modulates fibrosis and therapy response. Science Advances, 10 (27): eadl1197. ISSN 2375-2548

Astuti, Yuliana and Raymant, Meirion and Quaranta, Valeria and Clarke, Kim and Abudula, Maidinaimu and Smith, Olivia and Bellomo, Gaia and Chandran-Gorner, Vatshala and Nourse, Craig and Halloran, Christopher and Ghaneh, Paula and Palmer, Daniel and Jones, Robert P and Campbell, Fiona and Pollard, Jeffrey W and Morton, Jennifer P. and Mielgo, Ainhoa and Schmid, Michael C (2024) Author correction: Efferocytosis reprograms the tumor microenvironment to promote pancreatic cancer liver metastasis. Nature Cancer, 5: 808. ISSN 2662-1347

Astuti, Yuliana and Raymant, Meirion and Quaranta, Valeria and Clarke, Kim and Abudula, Maidinaimu and Smith, Olivia and Bellomo, Gaia and Chandran-Gorner, Vatshala and Nourse, Craig and Halloran, Christopher and Ghaneh, Paula and Palmer, Daniel and Jones, Robert P. and Campbell, Fiona and Pollard, Jeffrey W. and Morton, Jennifer P. and Mielgo, Ainhoa and Schmid, Michael C. (2024) Efferocytosis reprograms the tumor microenvironment to promote pancreatic cancer liver metastasis. Nature Cancer, 5. pp. 774-790. ISSN 2662-1347

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