The Effects of Ultrasound-Stimulated Microbubbles Combined with Radiotherapy in Cancer Models
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Embargo End Date
ICR Authors
Authors
Bargh-Dawson, H
Document Type
Thesis or Dissertation
Date
2025-01-06
Date Accepted
Abstract
Approximately 50% of all cancer patients are treated with radiotherapy during the course of their illness. Although progress has been made in treatment planning and delivery over recent decades, issues of normal tissue toxicities and radioresistance remain, particularly for patients with head and neck cancer (HNC). For these patients, there is a clinical unmet need for radiosensitising agents. Ultrasound-stimulated microbubbles (USMB) modulate the tumour microenvironment (TME) in a highly localised manner by targeting the microvasculature, inducing biological effects such as vessel disruption, vasodilation, immune cell activation and infiltration, and enhanced vessel permeability. Investigations into the use of USMB as an adjunct therapy for radiotherapy have reported enhanced tumour control in several preclinical xenograft models, however the mechanism responsible for the additive effects remains indeterminate. The aim of this thesis was to study the therapeutical potential of USMB as radiosensitisation agents in HNC using syngeneic preclinical models, and to explore the mechanism responsible for the radioenhancement effects. In vivo studies combining USMB and radiotherapy to treat two murine HNC models (MOC1 and MOC2) demonstrated the potential of the combination to enhance tumour growth control in this cancer indication. To evaluate the molecular and immunological effects and determine the mechanisms responsible for the radiosensitisation effect, multimodality imaging, histological analysis, immune profiling, and in vitro assays were carried out. The novel results from this thesis have the potential to optimise USMB use clinically to improve the quality of life of HNC patients following radiotherapy.
Citation
2025
DOI
Source Title
Publisher
Institute of Cancer Research (University Of London)
ISSN
eISSN
Collections
Research Team
Imaging Radiother Adapt