CCK-8 assay of XRCC4-depleted cancer cells overexpressing XRCC4 WT or XRCC4 Y66F mutant in multiple cisplatin concentrations (0, 2.5, 5, 10 μM) over 72 h further confirm that lactate-mediated NHEJ activation through XRCC4–LIG4 complex assembly is a key mechanism underlying chemoresistance (Figure 6C). Here, XRCC4 is linked to cancer.