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

Background: Neuroblastoma is the most common extra-cranial pediatric solid tumor.  ¹³¹ I-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. We aimed to study the impact of AURKA inhibitors on DNA damage and tumor cell death in combination with ¹³¹ I-MIBG therapy in a pre-clinical model of high-risk neuroblastoma.
Results: Using an in vivo model of high-risk neuroblastoma, we demonstrated a marked combinatorial effect of  ¹³¹ I-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  ¹³¹ I-MIBG treatment is active in resistant neuroblastoma models.
(© 2024. The Author(s).)