Tumour irradiation combined with vascular-targeted photodynamic therapy enhances antitumour effects in pre-clinical prostate cancer

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 us...

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Published in:British journal of cancer Vol. 125; no. 4; pp. 534 - 546
Main Authors: Sjoberg, Hanna T., Philippou, Yiannis, Magnussen, Anette L., Tullis, Iain D. C., Bridges, Esther, Chatrian, Andrea, Lefebvre, Joel, Tam, Ka Ho, Murphy, Emma A., Rittscher, Jens, Preise, Dina, Agemy, Lilach, Yechezkel, Tamar, Smart, Sean C., Kinchesh, Paul, Gilchrist, Stuart, Allen, Danny P., Scheiblin, David A., Lockett, Stephen J., Wink, David A., Lamb, Alastair D., Mills, Ian G., Harris, Adrian, Muschel, Ruth J., Vojnovic, Boris, Scherz, Avigdor, Hamdy, Freddie C., Bryant, Richard J.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 17.08.2021
Nature Publishing Group
Subjects:
631/67/1059/485
692/4028/546
Allografts
Animals
Biomedical and Life Sciences
Biomedicine
Cancer Research
Cell Line, Tumor
Clinical trials
Combined Modality Therapy
Dose Fractionation, Radiation
Drug Resistance
Epidemiology
Human Umbilical Vein Endothelial Cells
Humans
Magnetic resonance imaging
Male
Mice
Microenvironments
Molecular Medicine
Neovascularization, Pathologic - therapy
Oncology
Permeability
Photochemotherapy - methods
Photodynamic therapy
Prostate cancer
Prostatic Neoplasms - blood supply
Prostatic Neoplasms - therapy
Radiation therapy
Survival Analysis
Tumor Microenvironment
Tumors
Xenograft Model Antitumor Assays
ISSN:0007-0920, 1532-1827, 1532-1827
Online Access:Get full text
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Summary: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.
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ISSN:0007-0920
1532-1827
1532-1827
DOI:10.1038/s41416-021-01450-6