Novel Theranostic Targets for Prostate Cancer Beyond Prostate-Specific Membrane Antigen

Prostate-specific membrane antigen (PSMA)-targeted theranostics have transformed prostate cancer management, but some tumors exhibit low or heterogeneous PSMA expression, limiting eligibility and efficacy for radiopharmaceutical therapy. This review explores emerging biomarkers that may complement or expand beyond PSMA, including gastrin-releasing peptide receptor, fibroblast activation protein, prostate stem cell antigen, CD46, delta-like ligand 3, glypican-3, B7-H3, 6-transmembrane epithelial antigen of the prostate-1, trophoblast cell surface antigen-2, CEACAM5, and vicrostatin. We review their molecular biology, preclinical validation, clinical translation, and ongoing trials. These biomarkers represent diverse biological compartments, broadening the scope of precision radiotheranostics for prostate cancer.