Aurora Kinase A inhibition enhances DNA damage and tumor cell death with 131I-MIBG therapy in high-risk neuroblastoma.
Res Sq
; 2024 Jan 18.
Article
em En
| MEDLINE
| ID: mdl-38313265
ABSTRACT
Background:
Neuroblastoma is the most common extra-cranial pediatric solid tumor. 131I-metaiodobenzylguanidine (MIBG) is a targeted radiopharmaceutical highly specific for neuroblastoma tumors, providing potent radiotherapy to widely metastatic disease. Aurora kinase A (AURKA) plays a role in mitosis and stabilization of the MYCN protein in neuroblastoma. Here we explore whether AURKA inhibition potentiates a response to MIBG therapy.Results:
Using an in vivo model of high-risk neuroblastoma, we demonstrated a marked combinatorial effect of 131I-MIBG and alisertib on tumor growth. In MYCN amplified cell lines, the combination of radiation and an AURKA A inhibitor increased DNA damage and apoptosis and decreased MYCN protein levels.Conclusion:
The combination of AURKA inhibition with 131I-MIBG treatment is active in resistant neuroblastoma models and is a promising clinical approach in high-risk neuroblastoma.
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Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article