We demonstrate that SLC7A11-targeted inactivation (Figure 7B–7E), pretreatment with the xCT inhibitory compound erastin (Figure 3A, 3B, 3E, 3F; Figure 7A), and culture in cystine-free media (Figure 3C–3D) provide potent radiation sensitization of xCT+ tumor cells, in vitro and in xenograft. Here, SLC7A11 is linked to neoplasm.