Background:

• The FOLH1 gene encodes prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein that is highly expressed in most prostate cancer cells.
• PSMA expression can increase in metastatic castration resistant prostate cancer (mCPRC) but can be lost with the emergence of treatment-induced AR negative or neuroendocrine prostate cancer.
• PSMA is now a target for diagnostic imaging and treatment in prostate cancer. 177Lu-PSMA-617, a β-emitting PSMA targeted radioligand, has demonstrated improved survival for patients with mCRPC. Additionally, other novel therapeutics targeting PSMA including alternative radioligands, antibody drug conjugates, and bispecific antibodies are currently under development.
• Characterizing the molecular profile of high and low PSMA/FOLH1 expressing tumors will be critical to optimizing patients selection for PSMA targeted treatments