Fig. 1.

CSC hypothesis and the response of CSCs to radiotherapy. a In the CSC hypothesis, the CSC undergoes symmetrical or asymmetric division to give rise to two new CSCs or a differentiated daughter cell and another CSC. Based on the CSC model, the ability to initiate tumorigenesis and generate heterogeneity in primary tumours is fully attributed to the CSC population. b In response to radiotherapy, only if all CSCs are eliminated can tumours be permanently eradicated. Moreover, failed radiotherapy can “awaken” quiescent CSCs to enter the cell cycle, leading to tumour relapse, and induce them to transform into metastatic phenotypes, which can eventually result in tumour metastasis