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

## TL;DR

Combining Aurora Kinase A inhibition with 131I-MIBG therapy improves tumor cell death in high-risk neuroblastoma.

## Contribution

The study shows that AURKA inhibition enhances the effectiveness of 131I-MIBG in neuroblastoma treatment.

## Key findings

- AURKA inhibition combined with 131I-MIBG significantly reduced tumor growth in high-risk neuroblastoma models.
- The combination increased DNA damage and apoptosis in MYCN-amplified cell lines.
- MYCN protein levels were reduced with the combination therapy.

## Abstract

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.

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.

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.