Radiation-induced cell fate plasticity

Ionizing radiation (IR) is used to treat more than half of cancer patients because it induces DNA double-strand breaks and triggers apoptosis. IR also damages other nucleic acids, lipids, proteins and cellular organelles, initiating additional complex cellular responses. Some of these responses are transient, while others can become permanent and lead to changes in cellular identity. This review focuses on cell fate plasticity, defined as the conversion of one cell type into another, during recovery after IR-induced damage. We recognize that this process likely occurs along a continuum and may be reversible. We will distinguish cell fate plasticity from molecular or phenotypic plasticity, such as epigenetic modifications, transcriptomic shifts, altered signalling, morphological changes or acquisition of migratory behaviour, all of which are clinically relevant but do not constitute a change in cell type for the purposes of this review. Importantly, cell fate plasticity can enable cancer cells to acquire stem-like properties, which has major implications for tumour progression and therapy resistance.