Loading...
The approval of next-generation androgen receptor (AR)-directed therapies, such as abiraterone and enzalutamide, reinforced the critical role of the AR in metastatic castration-resistant prostate cancer. Although these are highly potent agents, resistance develops over time. One important resistance mechanism is the development of AR splice variants, which leads to AR variants that lack the ligand-binding domain, rendering them constitutively active, i.e., without requiring the AR for activation. With taxane chemotherapy, the primary mechanism of action is the induction of mitotic arrest by stabilizing microtubular function, but there is evidence to support direct AR inhibition by virtue of decreasing AR translocation into the nucleus.
Now, …