Six-transmembrane epithelial antigen of prostate 1 (STEAP1) (STEAP1)

Six-transmembrane epithelial antigen of prostate 1 (STEAP1) is a cell-surface protein primarily expressed in the prostate and highly upregulated in various malignancies, most notably metastatic castration-resistant prostate cancer (mCRPC) and Ewing sarcoma [4, 14]. Although it belongs to the STEAP family of metalloreductases, STEAP1 lacks the N-terminal NADPH-binding domain required for independent reductase activity; however, it is involved in iron and copper reduction and facilitates cell-cell communication through gap junction-like mechanisms [1, 12, 14]. The protein also modulates critical oncogenic signaling pathways, including PI3K/AKT, MAPK/ERK, and JAK/STAT, which promote tumor cell proliferation, survival, and epithelial-mesenchymal transition [1, 2, 16]. Its high tumor specificity and accessible cell-surface localization make it an ideal target for advanced therapeutic modalities such as antibody-drug conjugates (ADCs), bispecific T-cell engagers (TCEs), and CAR-T cell therapies [2, 3, 5]. Clinical candidates like xaluritamig (AMG 509) and vandortuzumab vedotin (DSTP3086S) have demonstrated the feasibility of targeting STEAP1 to induce immune-mediated or cytotoxic destruction of cancer cells [4, 7]. Despite its therapeutic potential, challenges remain in managing toxicities such as cytokine release syndrome and ensuring high selectivity to avoid affecting low-level expression in non-target tissues [4, 6].

Other names

STEAPPRSS24STEAP family member 1Metalloreductase STEAP1Six-transmembrane epithelial antigen of prostate 1

Antibody-drug conjugate (ADC) delivery of cytotoxic agents, T-cell redirection via bispecific T-cell engagers (TCEs), and Chimeric Antigen Receptor (CAR) T-cell mediated tumor lysis.