Here, we show that both cytosolic and nuclear roles of PCNA are affected; ATX-101 as a single agent induces apoptosis, stalls cancer cells in G2/M, reduces Akt/mTOR signaling and stemness of GICs, and when combined with RT, increases the level of γH2AX and DNA fragmentation and reduces the DNA damage response via reduction of DNA-PKcs. Here, AKT1 is linked to cancer.