在高危神经母细胞瘤中，极光激酶A抑制作用可增强I-美罗华治疗引发的DNA损伤和肿瘤细胞死亡。
Aurora Kinase A inhibition enhances DNA damage and tumor cell death with I-MIBG therapy in high-risk neuroblastoma.
作者信息
Kumar Prerna, Koach Jessica, Nekritz Erin, Mukherjee Sucheta, Braun Benjamin S, DuBois Steven G, Nasholm Nicole, Haas-Kogan Daphne, Matthay Katherine K, Weiss William A, Gustafson Clay, Seo Youngho
机构信息
University of Illinois College of Medicine at Peoria, Department of Pediatrics, Peoria, IL, United States.
University of California San Francisco, San Francisco, CA, United States.
出版信息
Res Sq. 2024 Jan 18:rs.3.rs-3845114. doi: 10.21203/rs.3.rs-3845114/v1.
BACKGROUND
Neuroblastoma is the most common extra-cranial pediatric solid tumor. 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. Here we explore whether AURKA inhibition potentiates a response to MIBG therapy.
RESULTS
Using an model of high-risk neuroblastoma, we demonstrated a marked combinatorial effect of I-MIBG and alisertib on tumor growth. In 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 I-MIBG treatment is active in resistant neuroblastoma models and is a promising clinical approach in high-risk neuroblastoma.
背景
神经母细胞瘤是最常见的儿童颅外实体瘤。碘-间位碘代苄胍（MIBG）是一种对神经母细胞瘤肿瘤具有高度特异性的靶向放射性药物，可为广泛转移的疾病提供有效的放射治疗。极光激酶A（AURKA）在神经母细胞瘤的有丝分裂和MYCN蛋白的稳定中发挥作用。在此，我们探讨AURKA抑制是否能增强对MIBG治疗的反应。
结果
使用高危神经母细胞瘤模型，我们证明了I-MIBG和阿利西替尼对肿瘤生长具有显著的联合作用。在MYCN扩增的细胞系中，放射治疗与AURKA抑制剂的联合使用增加了DNA损伤和细胞凋亡，并降低了MYCN蛋白水平。
结论
AURKA抑制与I-MIBG治疗的联合在耐药神经母细胞瘤模型中具有活性，是高危神经母细胞瘤一种有前景的临床治疗方法。
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