Enzalutamide induces cytotoxicity in desmoplastic small round cell tumor independent of the androgen receptor.
Commun Biol
; 7(1): 411, 2024 Apr 04.
Article
in En
| MEDLINE
| ID: mdl-38575753
ABSTRACT
Desmoplastic Small Round Cell Tumor (DSRCT) is a rare, pediatric cancer caused by the EWSR1WT1 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phenylthiohydantoin
/
Desmoplastic Small Round Cell Tumor
Limits:
Animals
/
Child
/
Female
/
Humans
/
Male
Language:
En
Journal:
Commun Biol
Year:
2024
Document type:
Article
Affiliation country:
Estados Unidos
Country of publication:
Reino Unido