Prostate-specific membrane antigen as target for vasculature-directed therapeutic strategies in solid tumors

Prostate-specific membrane antigen (PSMA) is one of the few biomarkers which has been successfully translated to the clinic as theranostic biomarker for patients with prostate cancer. In the context of prostate cancer, PSMA is overexpressed on the cell membrane of tumor cells, making it a viable target for interventions with urea-based small molecule inhibitors or antibodies conjugated to radioactive isotopes. Interestingly, in several non-prostatic cancers, expression of PSMA appears to be associated with the tumor neovasculature. This offers novel therapeutic opportunities for treatments targeting the vasculature in non-prostatic cancers. In this review, we discuss PSMA and its potential as target for vasculature-directed therapeutic approaches, including radioligand therapy, fusion protein vaccination and CAR T-cell therapy.