Understanding the role of indirect effects within radiotherapy

Abstract

Radiotherapy is well established as a cancer treatment modality and historically has been regarded as a simple treatment technique where a "block" of radiation is directed towards the solid tumour volume. However, in recent years, advances in research have revealed the highly complex nature of radiation response. Prominent amongst this research are cases of non-targeted radiation response where cells outside the irradiated volume have been shown to be effected by radiotherapy. For example bystander effects are noted as a short distance effect influencing cells located close to the irradiated region. This contrasts to radiotherapy induced immune responses that elicit metastatic regression in tumours located far away from the irradiated site.

RIBEs and abscopal effects do not fit with the at present well defined paradigms of radiation response where the chance of cell death is thought to increase exclusively with the dose delivered to a cell. These non-targeted radiation effects have only entered the field of radiation response in recent decades and so while the traditional understanding of radiation response has been characterised through methods like the LQ model, there exists no established methodology for quantifying the non-targeted effects of radiation. As part of this project we aim to gain a better understanding of radiation's non-targeted effects, with the target of creating a mathematical model capable of recreating the survival trends associated with these responses. Any mathematical modelling work will focus primarily on the role of RIBEs and consideration will be given to how these effects impact both in vitro and in vivo response. A particular focus will be given to the relevance of these effects in spatially fractionated exposures, where they'd be expected to be highly significant in determining cell survival.

As well as attempting to predict radiation response with a consideration for RIBEs another priority for this project is to gain a better understanding of the exact mechanisms underlying this response. The effects of RIBEs on out of field survival have been well documented, however, despite this, the mechanisms underlying these trends are yet to be elucidated, although many have been proposed. This project aims to investigate the role of the cGAS-STING pathway and dsDNA in transmission of the bystander effect.

Date of Award	Jul 2023
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Northern Ireland Department for the Economy
Supervisor	Stephen McMahon (Supervisor) & Kevin Prise (Supervisor)