GSE178406 The Androgen Receptor: A Therapeutic Target In Desmoplastic Small Round Cell Sarcoma

Contributors : Salah-Eddine Lamhamedi-Cherradi ; Brian A Menegaz ; Joseph A LudwigSeries Type : Protein profiling by protein arrayOrganism : Homo sapiensDesmoplastic small round cell tumor (DSRCT) is an aggressive, usually incurable sarcoma subtype that predominantly occurs in post-pubertal young males. Recent evidence suggests that the androgen receptor (AR) can promote tumor progression in DSRCTs. However, the mechanism of AR-induced oncogenic stimulation remains undetermined. Herein, we demonstrate that AR-directed antisense oligonucleotides (AR-ASO) block 5-dihydrotestosterone (DHT)-induced DSRCT cell proliferation and reduced xenograft tumor burden. RPPA analysis was performed to elucidate how AR signaling regulates cellular programs. To gain a preliminary understanding of the short-term pharmacodynamic effects of AR suppression, a group of JN-DSRCT xenografts was collected 10 days into their AR-ASO treatment for analysis by RPPA to assess early compensatory pharmacodynamic changes. Its blockade has long been of interest in managing prostate cancer, where a compensatory increase in AKT signaling has been reported following AR inhibition. Therefore, these results collectively validate another proof of concept of AR-based antisense activity in DSRCT and suggest a clinical path forward since the AR-ASO (AZD5312) was safe, and often effective, in PC patients (NCT03300505). Our findings have immediate clinical implications given the widespread availability of FDA-approved a...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Protein profiling by protein array Homo sapiens Source Type: research