Mixing, matching and modifying the prostate cancer microenvironment
Lu et al. (1) introduce a novel chimeric model of prostate cancer to interrogate the tumor microenvironment and signaling pathways in response to single targeting agents given alone or in combination with checkpoint inhibitors. This provides new preclinical data that reinforces clinical observations that combinatorial approaches for treating metastatic castration-resistant prostate cancer (mCRPC) may be more beneficial when compared with monotherapies (Figure 1). It also provides a rationale for the combination of biologic receptor and pathway targeting agents with the family of different checkpoint inhibitors. While the first demonstration of survival benefit by an immunotherapy for a solid tumor was in patients with minimally symptomatic or asymptomatic CRPC using an autologous dendritic cell product, sipuleucel-T (Provenge®) (3), immunotherapeutic approaches with single agent peptide or DNA vaccines using novel viral platforms, CAR T cells, and checkpoint inhibitors have all shown limited or minimal impact on the disease.