Radiation-induced bystander signalling in cancer therapy

It has become clear that cell–cell signalling — known as the bystander effect — has an important role in responses to ionizing radiation. What do we know about this effect and how might it affect the response to radiotherapy? Our understanding of how radiation kills normal and tumour cells has been based on an intimate knowledge of the direct induction of DNA damage and its cellular consequences. What has become clear is that, as well as responses to direct DNA damage, cell–cell signalling — known as the bystander effect — mediated through gap junctions and inflammatory responses may have an important role in the response of cells and tissues to radiation exposure and also chemotherapy agents. This Review outlines the key aspects of radiation-induced intercellular signalling and assesses its relevance for existing and future radiation-based therapies.