Aurora Kinase A inhibition enhances DNA damage and tumor cell death with ¹³¹I-MIBG therapy in high-risk neuroblastoma.

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.

Concl

SUBMITTER: Kumar P 

PROVIDER: S-EPMC10836112 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature