ScholarLink (思领科)
错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2024年6月13日

查看全文
  • Prerna Kumar,
  • Jessica Koach,
  • Erin Nekritz,
  • Sucheta Mukherjee,
  • Benjamin S. Braun,
  • Steven G. DuBois,
  • Nicole Nasholm,
  • Daphne Haas-Kogan,
  • Katherine K. Matthay,
  • William A. Weiss,
  • Clay Gustafson,
  • Youngho Seo

摘要

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. We aimed to study the impact of AURKA inhibitors on DNA damage and tumor cell death in combination with 131I-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 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.