Figure 1.

Radiation (RT)-induced cellular toxicity occurs through the production of double-stranded DNA break, which promptly activates a series of DNA damage response (DDR) that may repair the damage and rescue the cell from death through apoptosis, senescence, necrosis, mitotic catastrophe, and autophagy. Beyond DDR, the cell’s ability to survive from RT is also modulated by other biological pathways related to A) angiogenesis, B) cell cycle regulation, C) survival signaling, and D) cancer-host immune interaction. The activity of these pathways may be modulated by different targeted agents that in combination with RT may enhance the cytotoxicity of RT in soft-tissue sarcomas. DDR = DNA damage response; RT = radiotherapy.