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Updated: Jul 20, 2026
Quantification of Immunostained Caspase-9 in Retinal Tissue
Published on: July 25, 2022
Targeting caspase 8 to reduce the formation of metastases in neuroblastoma
1National 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
Abstract:
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.
Insights
Loss of caspase 8 (a protein regulating cell death) in neuroblastoma promotes metastasis and chemotherapy resistance. Restoring caspase 8 could be a promising therapeutic strategy for neuroblastoma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Neuroblastoma frequently presents with metastasis at diagnosis, posing a significant clinical challenge.
- Loss of caspase 8, a key protein in apoptosis, due to epigenetic methylation in neuroblastoma correlates with increased chemotherapy resistance.
Purpose of the Study:
- To investigate the role of caspase 8 in neuroblastoma metastasis.
- To evaluate caspase 8 as a potential therapeutic target for neuroblastoma, including primary tumors and metastatic lesions.
Main Methods:
- Analysis of caspase 8 expression and its correlation with clinical outcomes in neuroblastoma.
- Exploration of in vitro and in vivo methods to manipulate caspase 8 levels.
- Investigation of caspase 8 isoforms for potential therapeutic targeting.
Main Results:
- Epigenetic silencing of caspase 8 via methylation contributes to both chemotherapy resistance and a metastatic phenotype in neuroblastoma.
- Caspase 8 manipulation strategies have been developed for potential therapeutic applications.
Conclusions:
- Caspase 8 is a critical factor in neuroblastoma progression and chemoresistance.
- Targeting caspase 8 presents a promising therapeutic avenue for neuroblastoma, potentially impacting primary tumor growth and metastatic spread.
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