While a few in vivo studies evaluating SHP099 alone or combined SHP2/ALK inhibition have shown promising responses in a subset of neuroblastomas with NF1 loss (including several harboring ALK mutations), or in ALK- or ROS1-rearranged lymphomas and lung tumors, respectively (33, 34, 39, 41), thus far no preclinical drug combination evaluations have been conducted in ALK-missense mutant tumors, including neuroblastoma. This evidence concerns the gene PTPN11 and neuroblastoma.