In summary, this study defines a core epigenetic pathway, showing that increased SMARCA4 activity promotes luminal-to-neuroendocrine transformation by enhancing histone acetylation and chromatin accessibility at the PROX1 locus. Targeting the SMARCA4-PROX1 axis provides a valuable therapeutic strategy for combating enzalutamide resistance and NEPC progression.

P2, N=192, Recruiting, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine | Not yet recruiting --> Recruiting

When appended to the BET bromodomain inhibitor JQ1, this optimized handle yielded a potent and selective BRD4 degrader whose activity was dependent on RNF126. Importantly, transplantation of this handle onto a previously non-inhibitory ligand targeting the androgen receptor (AR) and its truncation variant, AR-V7, enabled selective degradation of both AR and AR-V7 in androgen-independent prostate cancer cells, thereby robustly inhibiting AR transcriptional activity beyond the established AR antagonist enzalutamide. Collectively, these findings demonstrate an optimized RNF126-based covalent handle for the rational development of molecular glue degraders against transcriptional regulators, including undruggable variants such as AR-V7.

This model can accurately predict the clinical prognosis of prostate cancer patients after surgery. Moreover, IGFBP3 can be used as a potential therapeutic target for ENZ resistance in prostate cancer.

P2, N=300, Not yet recruiting, Fudan University

P2, N=40, Recruiting, Icahn School of Medicine at Mount Sinai | Not yet recruiting --> Recruiting | Initiation date: Jun 2025 --> Mar 2026

P4, N=50, Recruiting, Bayer | Trial completion date: Jan 2026 --> Apr 2027 | Trial primary completion date: Jan 2026 --> Apr 2027

P1/2, N=32, Not yet recruiting, Amsterdam UMC Stichting | N=16 --> 32

P2, N=60, Not yet recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Functional validation demonstrated GRN's critical role in driving epithelial-mesenchymal transition in vitro and conferring resistance to enzalutamide (ENZ) in patient-derived organoids...Furthermore, we identified three novel stromal populations [decorin (DCN)+ endothelial cells, C-C motif chemokine ligand 7 (CCL7)+ fibroblasts, and interferon-induced protein with tetratricopeptide repeats 1 (IFIT1)+ neutrophils associated with disease relapse. These findings illuminate the tumor-immune crosstalk underlying treatment resistance and unveil promising therapeutic targets for overcoming lineage plasticity-driven resistance in advanced prostate cancer.

Enzalutamide (ENZ) and apalutamide (APA) are two second-generation androgen receptor inhibitors (SGARIs) that have been primarily used in the treatment of prostate cancer. In conclusion, functional modulation of androgen receptor signaling leads to significant alterations in male zebrafish behavior, particularly affecting fear responses, aggression, and anxiety-related behaviors. We believe that these findings could contribute to a deeper understanding of the relationship between androgens and behaviors in vertebrates, especially zebrafish.