STEAP1-4 (Six-Transmembrane Epithelial Antigen of the Prostate 1-4) and their Clinical Implications for Prostate Cancer

Abstract

Six-Transmembrane Epithelial Antigen of the Prostate 1-4 (STEAP1-4) compose a family of metalloproteinases involved in iron and copper homeostasis and other cellular processes. Thus far, five homologs are known: STEAP1, STEAP1B, STEAP2, STEAP3, and STEAP4. In prostate cancer, STEAP1, STEAP2, and STEAP4 are overexpressed while STEAP3 expression is downregulated. Although the metalloreductase activities of STEAP1-4 are well-documented, their other biological functions are not. Furthermore, the properties and expression levels of STEAP heterotrimers, homotrimers, heterodimers, and homodimers are not well-understood. Nevertheless, studies over the last few decades have provided sufficient impetus to investigate STEAP1-4 as potential biomarkers and therapeutic targets for prostate cancer. In particular, STEAP1 is the target of many emerging immunotherapies. Herein, we give an overview of the structure, physiology, and pathophysiology of STEAP1-4 to provide context for past and current efforts to translate STEAP1-4 into the clinic.

Bi-specific T-cell engagers (BiTEs) in prostate cancer and strategies to enhance development: hope for a BiTE-r future

“…Multiple alternative TAAs are under investigation as therapeutic targets in prostate cancer. One potential target proposed has been STEAP-1, which has some expression in lung tissue but otherwise has limited expression outside of the brain which is considered inaccessible to BiTE molecules (Xu et al, 2022). STEAP-1 has been targeted in a Phase 1 clinical trial using an agent called xaluritamig.…”