The Six-Transmembrane Epithelial Antigen of the Prostate (STEAP) protein family, comprising STEAP1, STEAP2, STEAP3, and STEAP4, plays a vital role in cellular metal homeostasis. These proteins are located on the cell membrane and are characterized by six transmembrane domains. With the exception of STEAP1, the STEAP proteins function as metal oxidoreductases due to their F420H2:NADP+ oxidoreductase (FNO)-like domain. However, STEAP1 contributes to metal metabolism through its heme group and interaction with other STEAP proteins. Beyond metal metabolism, STEAP proteins are involved in critical cellular processes, including the regulation of the cell cycle, proliferation, differentiation, and apoptosis.
STEAP proteins are recognized as potential biomarkers and therapeutic targets in human cancers, particularly prostate cancer:
STEAP1 belongs to the STEAP family of metalloreductases that has been reported to promote cancer cell proliferation, invasion, and epithelial-to-mesenchymal transition. It is highly expressed in >80% of metastatic castration-resistant prostate cancer with limited expression in normal human tissue, and has been associated with poor survival. Overexpression of STEAP1 in prostate tumors, combined with low or no expression on normal tissues, makes STEAP1 an ideal potential therapeutic target.
Large-scale genomic and proteomic efforts have identified STEAP2 (also known as STAMP1) as a superior prostate antigen for therapeutic targeting. Consistent with this discovery, it has been shown that STEAP2 expression is abundant across all stages of prostate cancer and can be used as a prognostic biomarker owing to its correlation with Gleason score.

