Tesson, M., Stevenson, K., Karim, S. A., Nixon, C., Chalmers, A. J. , Sansom, O. J., O'Neill, E., Jones, K. and Morton, J. P. (2024) Targeted irradiation in an autochthonous mouse model of pancreatic cancer. Disease Models and Mechanisms, 17(3), dmm050463. (doi: 10.1242/dmm.050463) (PMID:38421046) (PMCID:PMC10958199)
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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.
| Item Type: | Articles |
|---|---|
| Additional Information: | This work was supported by Cancer Research UK core funding to the CRUK Scotland Institute (A31287), to JPM (A29996) and to the CRUK Scotland Centre (CTRQQR-2021\100006), by a Cancer Research UK Precision Panc grant (A25233), and by Pancreatic Cancer UK (2021RIF_28_Morton). Work was also supported by the CRUK RadNet Glasgow centre (A28803). |
| Keywords: | General Biochemistry, Genetics and Molecular Biology, Immunology and Microbiology (miscellaneous), Medicine (miscellaneous), Neuroscience (miscellaneous) |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Nixon, Mr Colin and Tesson, Dr Mathias and O'Neill, Mr Eric and Chalmers, Professor Anthony and Morton, Dr Jennifer and Karim, Ms Saadia and Sansom, Professor Owen and Stevenson, Mrs Katrina |
| Creator Roles: | Tesson, M.Conceptualization, Methodology, Formal analysis, Investigation, Writing – original draft, Writing – review and editing, Visualization, Funding acquisition, Data curation Stevenson, K.Methodology, Investigation Karim, S.Investigation Nixon, C.Investigation Chalmers, A.Funding acquisition Sansom, O.Funding acquisition O'Neill, E.Methodology Morton, J.Conceptualization, Resources, Writing – original draft, Writing – review and editing, Visualization, Supervision, Funding acquisition |
| Authors: | Tesson, M., Stevenson, K., Karim, S. A., Nixon, C., Chalmers, A. J., Sansom, O. J., O'Neill, E., Jones, K., and Morton, J. P. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Disease Models and Mechanisms |
| Publisher: | Company of Biologists |
| ISSN: | 1754-8403 |
| ISSN (Online): | 1754-8411 |
| Published Online: | 29 February 2024 |
| Copyright Holders: | Copyright: © 2024 Published by The Company of Biologists Ltd. |
| First Published: | First published in Disease Models and Mechanisms 17(3): dmm050463 |
| Publisher Policy: | Reproduced under a Creative Commons licence |
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