The critical findings of this study are that (S)-crizotinib: (a) effectively reduced GC cell viability, promoted apoptosis, induced cell cycle arrest, and decreased xenograft GC tumor growth; (b) inhibited GC cell growth through a mechanism of oxidative DNA damage independent of MTH1 inhibition; and (c) activated the pro-survival Akt–ATM pathway, whose inhibition further enhanced the anti-cancer activity of (S)-crizotinib (Figure S12). Here, ATM is linked to cancer.