在高危神经母细胞瘤中，极光激酶A抑制与I-间碘苄胍疗法联合可增强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
Department of Pediatrics, University of Illinois College of Medicine at Peoria, 530 NE Glen Oak Ave, Peoria, IL, 61637, USA.
Department of Pediatrics, University of California, San Francisco, CA, USA.
出版信息
EJNMMI Res. 2024 Jun 13;14(1):54. doi: 10.1186/s13550-024-01112-7.
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. We aimed to study the impact of AURKA inhibitors on DNA damage and tumor cell death in combination with 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 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 I-MIBG treatment is active in resistant neuroblastoma models.
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，可对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蛋白的稳定中起作用。我们旨在研究在高危神经母细胞瘤的临床前模型中，AURKA抑制剂与I-MIBG治疗联合使用对DNA损伤和肿瘤细胞死亡的影响。
结果
使用高危神经母细胞瘤的体内模型，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，放疗与AURKA A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。
Zotero 插件