Figure 4: A proposed model for radiotherapy approaches that can target CSCs. (A) In traditional radiotherapy, the bulk tumor shrinks after initial radiation, but the cancer cells repopulate during the gaps of radiotherapy, leading to patient relapse. (B) In combinatorial radiotherapy, drugs or inhibitors can be used to sensitize CSCs to radiation and enhance the outcome of therapy. During initial radiotherapy, the main targets may be the quiescent status of CSCs and hypoxia. Afterwards, the DNA repair mechanisms and the survival pathways become more dominant and can be targeted to prevent the repopulation of CSCs.