PSMA/STEAP1

OVERVIEW

Prostate-Specific Membrane Antigen (PSMA) is a type II transmembrane glycoprotein encoded by the Folate Hydrolase (FOLH1) gene.1

Six Transmembrane Epithelial Antigen of the Prostate 1 (STEAP1) is a cell surface antigen expressed at cell-cell junctions.2


IMPLICATIONS IN CANCER

PSMA has been used extensively as a marker and a target for prostate cancer3 PSMA is overexpressed in 90% of metastatic prostate cancer and has low levels of expression in healthy tissues. However, PSMA can be heterogeneous in metastatic castration-resistant prostate cancer (mCRPC), and some mCRPC are negative for PSMA, hence the benefit of a second target.

STEAP1 was identified as one of the most highly enriched cell surface antigens from cell surface proteomic profiling of human prostate adenocarcinoma cell lines.2,3 STEAP1 is overexpressed in more than 80% of mCRPC. The broad, homogenous expression of STEAP1 makes it an appealing target for mCRPC

  1. Giraudet AL, et al. PSMA targeting in metastatic castration-resistant prostate cancer: where are we and where are we going? Ther Adv Med Oncol. 2021;Oct 26(13):17588359211053898. 
  2. Bhatia V, et al. Targeting advanced prostate cancer with STEAP1 chimeric antigen receptor T cell and tumor-localized IL-12 immunotherapy. Nat Commun. 2023;(14):2041.
  3. Nakamura H, et al. Targeting STEAP1 as an anticancer strategy. Front Oncol. 2023;Oct 16(13):1285661.