Targeting caspase 8 to reduce the formation of metastases in neuroblastoma

The clinical challenge in neuroblastoma is the presence of metastasis at diagnosis in the majority of patients. Caspase 8 is an integral protein in death receptor-associated apoptosis, and loss of caspase 8 via the epigenetic phenomenon of methylation in neuroblastoma has led to increased resistance to chemotherapy. Recent evidence suggests that caspase 8 loss may also contribute to a metastatic phenotype; thus, caspase 8 may prove to be an attractive target for therapy both in treating primary tumours as well as preventing and treating metastatic lesions. Numerous methods have been described to manipulate caspase 8 levels both in vitro and in vivo, and investigation into caspase 8 isoforms may also bring forth additional therapeutic targets.