The mechanisms underlying GRP78-mediated radioresistance involve the inhibition of apoptosis where GRP78 suppresses apoptotic signaling by modulating pro-survival pathways, including PI3K/AKT and NF-κB, preventing radiation-induced cell death [224] and the activation of pro-survival autophagy, where the radiation-induced ER stress activates autophagy via GRP78, providing an alternative survival mechanism for cancer cells [225]. This evidence concerns the gene HSPA5 and cancer.