CCN3-EZH2-AR feedback loop: new targets for enzalutamide and castration resistant prostate cancer

The development of castration resistant prostate cancer and anti-androgen resistance remains one of the largest hurdles in the successful treatment of prostate cancer. Therefore, the identification of dysregulated pathways contributing to this resistance and determining ways to target these mechanisms is of utmost importance. In the recent publication in Cancer Research, Fong et al. identify a novel role for cytoplasmic CCN3 in prostate cancer progression and enzalutamide resistance. The authors demonstrate that CCN3 expression inhibits androgen receptor signaling and thereby suppresses enzalutamide-resistant prostate cancer cell proliferation, colony formation, and xenograft tumor growth. The data from this manuscript highlight an intriguing potential therapeutic target for the treatment of CRPC and are a critical step forwards towards treating enzalutamide resistant prostate cancer.