Beyond the Target: A Review of Radiation-Induced Bystander Effects in Radiobiology and Radiation Therapy

Radiation-induced bystander effects (RIBEs) are a well-known phenomenon in radiobiology that shows the impact of radiation outside the cells that are immediately irradiated. However, the understanding of RIBE in radiation therapy (RT) is still in the exploratory segment. It can reveal the intrinsic heterogeneity of the crosstalk between normal and cancerous tissues. Bystander effects cause DNA damage and altered gene expression in neighbouring cells, revealing complex signalling pathways between irradiated and unirradiated cells. Utilizing RIBE findings in the context of RT, methodologies consisting of FLASH radiotherapy and microbeam radiation therapy (MRT) are being developed. The intention is to balance unique cellular targeting against cancer as well as protecting normal tissues. In this review, we summarize the state-of-the-art knowledge of RIBE mechanisms in radiobiology, present an overview of existing and potential study methods, and review pioneer clinical studies in RT and RIBE-related clinical trials.