Prostate-specific membrane antigen (PSMA), also known as glutamate carboxypeptidase II (GCPII) or folate hydrolase 1 (FOLH1), is a transmembrane glycoprotein expressed predominantly in prostate epithelial cells. Structurally, it contains a short intracellular domain, a transmembrane region, and a large extracellular enzymatic domain with zinc-dependent hydrolase activity. While its physiological role remains incompletely understood, PSMA is implicated in folate metabolism, nutrient uptake, and cell signaling pathways.
PSMA gained prominence due to its overexpression in prostate cancer cells, particularly in advanced, metastatic, or androgen-resistant cases. Its expression correlates with tumor aggressiveness, making it a valuable biomarker and therapeutic target. Notably, PSMA is not exclusive to prostate cancer; low levels are found in some healthy tissues (e.g., salivary glands, kidneys), and aberrant expression occurs in other cancers, including renal, bladder, and glioblastoma.
In diagnostics, PSMA-targeted antibodies enable advanced imaging techniques like PSMA-PET scans to detect metastases. Therapeutically, anti-PSMA antibodies are engineered into antibody-drug conjugates (ADCs), bispecific antibodies, or CAR-T cell therapies. Radioligand therapies (e.g., ¹⁷⁷Lu-PSMA-617) exploit PSMA's internalization capability to deliver targeted radiation. Challenges include managing heterogeneous PSMA expression, off-target effects, and resistance mechanisms. Ongoing research focuses on optimizing antibody affinity, reducing toxicity, and expanding applications to non-prostate malignancies.