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.
McKee
Amy E
AE
National Cancer Institute, NIH, Cell & Molecular Biology Section, Paediatric Oncology Branch, 10 Center Drive, Building 10/CRC, Room 1-5816, Bethesda, MD 20892, USA. mckeea@mail.nih.gov
Thiele
Carol J
CJ
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism* / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D009447:Neuroblastoma / Q000188:drug therapy / Q000201:enzymology* / Q000517:prevention & control / Q000556:secondary*
D000970:Antineoplastic Agents; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases