Cell-surface targets for prostate cancer therapeutics

This review highlights recent data regarding antigens on the cell surface of prostate cancer cells or cells in the prostate cancer tumor microenvironment which may serve as targets for novel therapeutics. Emphasis is placed on clinical data involving human subjects. The biological role of each antigen discussed is described, as are the expression patterns of the antigen in relation to histologic subtype of prostate cancer. Most descriptions are based on histological or genomic data, and quantitative assessment via targeted immuno-PET when available. Some antigens such as prostate-specific membrane antigen (PSMA), TROP-2, six-transmembrane epithelial antigen of the prostate 1 (STEAP1), and PSCA are overexpressed primarily in prostate adenocarcinoma, while CEACAM5 or delta-like ligand 3 (DLL3) are more commonly expressed in neuroendocrine prostate cancer. CD46 may be overexpressed in both prostate adenocarcinoma and neuroendocrine prostate cancer. The expression pattern and relevance of human epidermal growth factor receptor 2 (HER2) as a therapeutic target in prostate cancer remains unclear. Fibroblast activation protein (FAP) is a cell-surface proteins more often expression on cancer fibroblasts in the tumor microenvironment. Ongoing investigation into novel targets for the treatment of prostate cancer continues to identify promising antigens which are overexpressed on the cell surface. Patterns of expression may vary based on histologic type, anatomic location, and treatment state of prostate cancer, and these factors will ultimately dictate the utility of novel therapeutic agents that are in development.