Targeting inflammatory cytokines-androgen receptor (AR) signaling with ASC-J9 to better battle prostate cancer progression.

Inflammatory cytokines and chemokines released by macrophages in the prostate cancer microenvironment may signal via the androgen receptor (AR) to influence tumor progression. In particular, macrophages appear to promote tumorigenesis by altering the chemokine (C-C motif) ligand 4 (CCL4)/AR signaling axis. This process can be blocked by ASC-J9, an enhancer of AR degradation. ASC-J9 also inhibits the CCL2-dependent, signal transducer and activator of transcription 3 (STAT3)-mediated pro-metastatic signaling cascade that is generally activated by androgen deprivation therapy. Thus, targeting inflammatory cytokines signaling via the AR, with ASC-J9, represents a promising therapeutic approach against prostate cancer progression.