Although early phase clinical trials of first- and second-generation ALK inhibitors showed modest efficacy of the first-generation inhibitor crizotinib in NB with F1174 hotspot mutations being resistant,44 third-generation ALK inhibitors such as lorlatinib exhibit improved efficacy alone and when combined with chemotherapy.28,44-46 Crizotinib is currently being administered with chemotherapy in a phase III upfront trial for patients with HR-NB with ALK alterations (ClinicalTrials.gov: NCT03126916). Here, ALK is linked to neuroblastoma.