These murine Trp53 wt and mutant TH-MYCN cell lines are useful syngeneic, immunocompetent neuroblastoma models, the former to test p53-dependent therapies in combination with immunotherapies, such as anti-GD2, and the latter as models of chemoresistant relapsed neuroblastoma when aberrations in the p53 pathway are more common.
Though primary NBs largely with wild-type p53 respond well to interventions, dysfunctional signaling in the p53 pathways in a MYCN oncogene driven background is found in a number of children with NB.
As p53 loss of function (LOF) confers high-level drug resistance in neuroblastoma, p53-independent therapies might have superior activity in recurrent neuroblastoma.
If these data are confirmed in neuroblastoma tumors, this suggests that p53-independent therapy and reactivation of inactive p53 approaches would be useful in the management of relapsed neuroblastoma.