@article {3182026,
	title = {Intracranial Assessment of Androgen Receptor Antagonists in Mice Bearing Human Glioblastoma Implants},
	journal = {International Journal of Molecular Sciences},
	volume = {25},
	year = {2023},
	pages = {332},
	abstract = {The median survival time of patients with an aggressive brain tumor, glioblastoma, is still poor due to ineffective treatment. The discovery of androgen receptor (AR) expression in 56\% of cases offers a potential breakthrough. AR antagonists, including bicalutamide and enzalutamide, induce dose-dependent cell death in glioblastoma and glioblastoma-initiating cell lines (GIC). Oral enzalutamide at 20 mg/kg reduces subcutaneous human glioblastoma xenografts by 72\% (p\&nbsp;= 0.0027). We aimed to further investigate the efficacy of AR antagonists in intracranial models of human glioblastoma. In U87MG intracranial models, nude mice administered Xtandi (enzalutamide) at 20 mg/kg and 50 mg/kg demonstrated a significant improvement in survival compared to the control group (p\&nbsp;= 0.24 and\&nbsp;p\&nbsp;\&lt; 0.001, respectively), confirming a dose{\textendash}response relationship. Additionally, we developed a newly reformulated version of bicalutamide, named {\textquotedblleft}soluble bicalutamide (Bic-sol){\textquotedblright}, with a remarkable 1000-fold increase in solubility. This reformulation significantly enhanced bicalutamide levels within brain tissue, reaching 176\% of the control formulation{\textquoteright}s area under the curve. In the U87MG intracranial model, both 2 mg/kg and 4 mg/kg of Bic-sol exhibited significant efficacy compared to the vehicle-treated group (p\&nbsp;= 0.0177 and\&nbsp;p\&nbsp;= 0.00364, respectively). Furthermore, combination therapy with 8 mg/kg Bic-sol and Temozolomide (TMZ) demonstrated superior efficacy compared to either Bic-sol or TMZ as monotherapies (p\&nbsp;= 0.00706 and\&nbsp;p\&nbsp;= 0.0184, respectively). In the ZH-161 GIC mouse model, the group treated with 8 mg/kg Bic-sol as monotherapy had a significantly longer lifespan than the groups treated with TMZ or the vehicle (p\&nbsp;\&lt; 0.001). Our study demonstrated the efficacy of androgen receptor antagonists in extending the lifespan of mice with intracranial human glioblastoma, suggesting a promising approach to enhance patient outcomes in the fight against this challenging disease.},
	url = {https://doi.org/10.3390/ijms25010332},
	author = {Nomi Zalcman and Liraz Larush and Haim Ovadia and Hanna Charbit and Shlomo Magdassi and Iris Lavon}
}
