Inducing Mitotic Catastrophe as a Therapeutic Approach to Improve Outcomes in Ewing Sarcoma.
Aurora kinase A
Ewing sarcoma
SB-743921
VIC-1911
drug synergy
kinesin family member 11
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
10 Oct 2023
10 Oct 2023
Historique:
received:
11
09
2023
revised:
03
10
2023
accepted:
07
10
2023
medline:
28
10
2023
pubmed:
28
10
2023
entrez:
28
10
2023
Statut:
epublish
Résumé
Ewing sarcoma (EWS) is an aggressive pediatric malignancy of the bone and soft tissues in need of novel therapeutic options. To identify potential therapeutic targets, we focused on essential biological pathways that are upregulated by EWS-FLI1, the primary oncogenic driver of EWS, including mitotic proteins such as Aurora kinase A (AURKA) and kinesin family member 15 (KIF15) and its binding partner, targeting protein for Xklp2 (TPX2). KIF15/TPX2 cooperates with KIF11, a key mitotic kinesin essential for mitotic spindle orientation. Given the lack of clinical-grade KIF15/TPX2 inhibitors, we chose to target KIF11 (using SB-743921) in combination with AURKA (using VIC-1911) given that phosphorylation of KIF15
Identifiants
pubmed: 37894278
pii: cancers15204911
doi: 10.3390/cancers15204911
pmc: PMC10605681
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Braden's Hope for Childhood Cancer
ID : n/a
Organisme : Noah's Bandage
ID : n/a
Organisme : Kansas Institute for Precision Medicine
ID : GM130423
Organisme : KUMC Biomedical Training Research Fellowship
ID : n/a
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