We designed a second study to further explore the combination of CX-5461 with TOP1 inhibitors, combining CX-5461 with two 2-drug salvage combinations used in relapsed and refractory neuroblastoma, which have been used as backbones for incorporating new agents in clinical trials: irinotecan + temozolomide and topotecan + cyclophosphamide (Fig. 7K; Supplementary Data Tables S7, S8)50,51. The gene discussed is TOP1; the disease is neuroblastoma.