In order to assess whether treatment with SETD8 inhibitors (SGSS05-NS3 or UNC0379) could sensitize NB cells to DDR-inducing drugs, we performed a chemical screen evaluating synergy scores, including Bliss and HSA, obtained from the combination of different concentrations of Topotecan (0.1–30 nM), a topoisomerase inhibitor, and SGSS05-NS3 or UNC0379 (0.1–30 μM), in 5 NB cells (2 MYCN-WT, SY5Y and NBLS, and 3 MYCN-amplified, IMR32, SAN and KCNR) (Fig. 7A and Figure S7A). This evidence concerns the gene KMT5A and neuroblastoma.