FIGURE 3.

Reversal of radioresistance by targeting ferroptosis. Radioresistance remains a major factor in radiotherapy failure. Radiation therapy can lead to the production of massive ROS and upregulate the expression of ACSL4, promote lipid peroxidation and eventually cause ferroptosis. However, radiotherapy also induced an adaptive response in tumor cells. The expression of ferroptosis suppressors, including SLC7A11 and GPX4, was also significantly upregulated, which promoted cancer cell survival and radioresistance after radiotherapy. FINs that inhibit SLC7A11 or GPX4 can enhance the sensitivity of radioresistant cancer cells to IR-induced ferroptosis and reverse radioresistance. miR-7-5p controls radioresistance via ROS generation that leads to ferroptosis. Knockdown of miR-7-5p increased ROS and reversed radioresistance.