Journal article
Tumour irradiation combined with vascular-targeted photodynamic therapy enhances anti-tumour effects in preclinical prostate cancer
- Abstract:
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Background: There is a need to improve the treatment of prostate cancer (PCa) and reduce treatment side effects. Vascular-targeted photodynamic therapy (VTP) is a focal therapy for low-risk low-volume localised PCa, which rapidly disrupts targeted tumour vessels. There is interest in expanding the use of VTP to higher-risk disease. Tumour vasculature is characterised by vessel immaturity, increased permeability, aberrant branching and inefficient flow. FRT alters the tumour microenvironment and promotes transient ‘vascular normalisation’. We hypothesised that multimodality therapy combining fractionated radiotherapy (FRT) and VTP could improve PCa tumour control compared against monotherapy with FRT or VTP.
Methods: We investigated whether sequential delivery of FRT followed by VTP 7 days later improves flank TRAMP-C1 PCa tumour allograft control compared to monotherapy with FRT or VTP.
Results: FRT induced ‘vascular normalisation’ changes in PCa flank tumour allografts, improving vascular function as demonstrated using dynamic contrast-enhanced magnetic resonance imaging. FRT followed by VTP significantly delayed tumour growth in flank PCa allograft pre-clinical models, compared with monotherapy with FRT or VTP, and improved overall survival.
Conclusion: Combining FRT and VTP may be a promising multimodal approach in PCa therapy. This provides proof-of-concept for this multimodality treatment to inform early phase clinical trials.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 4.1MB, Terms of use)
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- Publisher copy:
- 10.1038/s41416-021-01450-6
Authors
- Publisher:
- Springer Nature
- Journal:
- British Journal of Cancer More from this journal
- Volume:
- 125
- Issue:
- 2021
- Pages:
- 534–546
- Publication date:
- 2021-06-21
- Acceptance date:
- 2021-05-25
- DOI:
- EISSN:
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1532-1827
- ISSN:
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0007-0920
- Language:
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English
- Keywords:
- Pubs id:
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1178794
- Local pid:
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pubs:1178794
- Deposit date:
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2021-05-26
- ARK identifier:
Terms of use
- Copyright holder:
- Sjoberg et al.
- Copyright date:
- 2021
- Rights statement:
- © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
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