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

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

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.

Afiliação

Kumar P; Department of Pediatrics, University of Illinois College of Medicine at Peoria, 530 NE Glen Oak Ave, Peoria, IL, 61637, USA. prerna@uic.edu.
Koach J; Department of Pediatrics, University of California, San Francisco, CA, USA. prerna@uic.edu.
Nekritz E; Department of Pediatrics, University of California, San Francisco, CA, USA.
Mukherjee S; Department of Pediatrics, University of California, San Francisco, CA, USA.
Braun BS; Department of Pediatrics, University of California, San Francisco, CA, USA.
DuBois SG; Department of Pediatrics, University of California, San Francisco, CA, USA.
Nasholm N; Helen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, CA, USA.
Haas-Kogan D; Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA, USA.
Matthay KK; Department of Pediatrics, University of California, San Francisco, CA, USA.
Weiss WA; Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Gustafson C; Department of Pediatrics, University of California, San Francisco, CA, USA.
Seo Y; Helen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, CA, USA.

EJNMMI Res ; 14(1): 54, 2024 Jun 13.

Article em En | MEDLINE | ID: mdl-38869684

ABSTRACT

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.

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.