Prostate cancer is the second most common malignancy diagnosed in men and the sixth highest contributor to cancer-related mortality worldwide (1). Advanced prostate cancer initially responds to androgen deprivation therapy before progression to an incurable state termed metastatic castration resistant prostate cancer (mCRPC). mCRPC is typically treated with taxanes or androgen receptor (AR) pathway inhibitors, but the survival benefit is variable and often brief (2). In recent years, focus has turned to the development of therapies outside of the AR signaling pathway. PARP inhibitors and pembrolizumab are effective in the subset of mCRPC with homologous recombination repair and mismatch repair defects, respectively (3,4). Further agents including PSMA-lutetium-177, DNA peptide-based vaccines, and oncolytic viruses are in various stages of clinical development (3). While single agent immune checkpoint blockade (ICB) has proved relatively ineffective in unselected mCRPC, in this commentary, we highlight its potential for eliciting potent anti-tumor responses when combined with agents that target the uniquely immunosuppressive tumor microenvironment (TME) of mCRPC.
Journal
Translational Andrology and Urology