Enzalutamide induces cytotoxicity in desmoplastic small round cell tumor independent of the androgen receptor.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
04 Apr 2024
04 Apr 2024
Historique:
received:
02
11
2023
accepted:
01
03
2024
medline:
5
4
2024
pubmed:
5
4
2024
entrez:
4
4
2024
Statut:
epublish
Résumé
Desmoplastic Small Round Cell Tumor (DSRCT) is a rare, pediatric cancer caused by the EWSR1::WT1 fusion protein. DSRCT predominantly occurs in males, which comprise 80-90% of the patient population. While the reason for this male predominance remains unknown, one hypothesis is that the androgen receptor (AR) plays a critical role in DSRCT and elevated testosterone levels in males help drive tumor growth. Here, we demonstrate that AR is highly expressed in DSRCT relative to other fusion-driven sarcomas and that the AR antagonists enzalutamide and flutamide reduce DSRCT growth. However, despite these findings, which suggest an important role for AR in DSRCT, we show that DSRCT cell lines form xenografts in female mice at the same rate as male mice and AR depletion does not significantly alter DSRCT growth in vitro. Further, we find that AR antagonists reduce DSRCT growth in cells depleted of AR, establishing an AR-independent mechanism of action. These findings suggest that AR dependence is not the reason for male predominance in DSRCT and that AR-targeted therapies may provide therapeutic benefit primarily through an AR-independent mechanism that requires further elucidation.
Identifiants
pubmed: 38575753
doi: 10.1038/s42003-024-06003-0
pii: 10.1038/s42003-024-06003-0
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
411Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : 1R01CA222856
Informations de copyright
© 2024. The Author(s).
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