The majority of CRPC bone metastases (80%) was defined as AR-driven based on PCA analysis and high expression of the AR, AR co-regulators (FOXA1, HOXB13), and AR-regulated genes (KLK2, KLK3, NKX3.1, STEAP2, TMPRSS2); 20% were non-AR-driven.
An exploratory endpoint was the association of Triptocare baseline variables (including TMPRSS2-ERG and PCA3 scores) and PCA3 score at Triptocare last value available with CRPC onset.
The ability of BET family inhibitor ABBV-075 to inhibit transcription activation downstream of the initiating events of transcription factors like AR and TMPRSS2:ETS fusion proteins provides a promising therapeutic option for CRPC patients who have developed resistance to second-generation antiandrogens.
We hypothesize that TMPRSS2-ERG fusions regulate androgen biosynthetic enzyme (ABE) gene expression and the production of androgens, which contributes to the development of CRPC.
As surrogate for CTCs we measured KLK3, PCA3, and TMPRSS2-ERG messenger RNA (mRNA) in the peripheral blood mononuclear cell (PBMC) fraction from a castration-resistant prostate cancer (CRPC) patient cohort and three control groups.
The expression level of the TMPRSS2-ERG gene was studied in various histological grades of prostate cancer and castration-resistant prostate cancer (CPRC).
Similarly, we demonstrate that ETS2, which is deleted in approximately one-third of CRPCs (commonly through TMPRSS2:ERG fusions), is also deregulated through mutation.
The TMPRSS2-ERG expressing DuCaP-N cell line represents human prostate cancer prior to endocrine treatment, and its parental DuCaP cell line is a model for CRPC.
Its relevance in castration-resistant prostate cancer (CRPC) remains controversial as ERG is not expressed in some TMPRSS2-ERG androgen-independent xenograft models.