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

Hanna T. Sjoberg, Yiannis Philippou, Anette L. Magnussen, Iain D.C. Tullis, Esther Bridges, Andrea Chatrian, Joel Lefebvre, Ka Ho Tam, Emma A. Murphy, Jens Rittscher, Dina Preise, Lilach Agemy, Tamar Yechezkel, Sean C. Smart, Paul Kinchesh, Stuart Gilchrist, Danny P. Allen, David A. Scheiblin, Stephen J. Lockett, David A. WinkAlastair D. Lamb, Ian G. Mills, Adrian Harris, Ruth J. Muschel, Boris Vojnovic, Avigdor Scherz, Freddie C. Hamdy, Richard J. Bryant*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

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.

Original languageEnglish
Pages (from-to)534-546
Number of pages13
JournalBritish Journal of Cancer
Volume125
DOIs
Publication statusPublished - 21 Jun 2021

Bibliographical note

Funding Information:
Funding information This work was funded by a Cancer Research UK/Royal College of Surgeons of England Clinician Scientist Fellowship (reference C39297/A22748, for R.J.B. and H.S.), and by a research grant from The Urology Foundation (for Y.P.), along with a Cancer Research UK Clinical Research Training Fellowship (for Y.P.). B.V. and I.D.C.T. were funded by a Cancer Research UK program grant (C5255/A12678). J.L. was supported by a FRQNT postdoctoral scholarship (reference 257844). A.M. was funded by the John Fell Fund and the John Black Charitable Foundation. The authors also acknowledge Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. 75N91019D00024. The content of this publication does neither necessarily reflect the views or policies of the Department of Health and Human Services nor does mention of trade names, commercial products or organisations imply endorsement by the U.S. Government.

Publisher Copyright:
© 2021, The Author(s).

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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