PSCA, short for Prostate Stem Cell Antigen, is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein. It has diverse functions in different tissues, being involved in processes like cell proliferation where it can have both inhibitory and tumor-inducing roles. PSCA may regulate the IL-6 expression through the p38/NF-κB signaling pathway in prostate cancer cells, influencing cell invasion and metastasis [4].

PSCA has emerged as a potential therapeutic target in multiple cancers. In pancreatic cancer, human iPSC-derived CAR macrophages targeting PSCA (CAR-iMacs) show strong antitumor activity in vitro and in vivo, reducing tumor burden and improving survival in mouse models [1]. In metastatic castration-resistant prostate cancer, a phase 1 trial of PSCA-directed CAR T cells has been carried out, with some patients showing prostate-specific antigen declines and radiographic improvements [2]. In gastric cancer, anti-PSCA CAR-T cells exhibit robust anti-tumor cytotoxicity in vitro and can stunt tumor progression in vivo when delivered by peritumoral injection [6]. Also, PSCA gene variants are associated with the risk of cancers like gastric and bladder cancer, as well as non-neoplastic diseases such as gastritis, duodenal ulcer, and gastric ulcer [3,5,7].

In conclusion, PSCA is a cell-surface protein with complex functions in different tissues. Research using in vivo models like mouse models for pancreatic, prostate, and gastric cancer has revealed its significance as a therapeutic target in these cancers. Additionally, the association of its gene variants with cancer and non-neoplastic diseases highlights its importance in understanding disease pathogenesis and developing potential preventive and treatment strategies.

References:

1. Shah, Zahir, Tian, Lei, Li, Zhixin, Caligiuri, Michael A, Yu, Jianhua. 2024. Human anti-PSCA CAR macrophages possess potent antitumor activity against pancreatic cancer. In Cell stem cell, 31, 803-817.e6. doi:10.1016/j.stem.2024.03.018. https://pubmed.ncbi.nlm.nih.gov/38663406/

2. Dorff, Tanya B, Blanchard, M Suzette, Adkins, Lauren N, Forman, Stephen J, Priceman, Saul J. 2024. PSCA-CAR T cell therapy in metastatic castration-resistant prostate cancer: a phase 1 trial. In Nature medicine, 30, 1636-1644. doi:10.1038/s41591-024-02979-8. https://pubmed.ncbi.nlm.nih.gov/38867077/

3. Cui, Huijie, Tang, Mingshuang, Zhang, Min, Gu, Dongqing, Zhang, Ben. . Variants in the PSCA gene associated with risk of cancer and nonneoplastic diseases: systematic research synopsis, meta-analysis and epidemiological evidence. In Carcinogenesis, 40, 70-83. doi:10.1093/carcin/bgy151. https://pubmed.ncbi.nlm.nih.gov/30407486/

4. Liu, Luhao, Li, Ermao, Luo, Lianmin, Luo, Jintai, Zhao, Zhigang. 2017. PSCA regulates IL-6 expression through p38/NF-κB signaling in prostate cancer. In The Prostate, 77, 1389-1400. doi:10.1002/pros.23399. https://pubmed.ncbi.nlm.nih.gov/28845520/

5. Wang, Xiao-Feng, Liu, Dong-Li, Geng, Li. . The PSCA rs2294008 (C/T) Polymorphism Increases the Risk of Gastric and Bladder Cancer: A Meta-Analysis. In Genetic testing and molecular biomarkers, 27, 44-55. doi:10.1089/gtmb.2022.0067. https://pubmed.ncbi.nlm.nih.gov/36853840/

6. Wu, Di, Lv, Jiang, Zhao, Ruocong, Li, Peng, Yao, Yao. 2020. PSCA is a target of chimeric antigen receptor T cells in gastric cancer. In Biomarker research, 8, 3. doi:10.1186/s40364-020-0183-x. https://pubmed.ncbi.nlm.nih.gov/32010446/

7. Usui, Yoshiaki, Matsuo, Keitaro, Oze, Isao, Kubo, Michiaki, Wakai, Kenji. 2019. Impact of PSCA Polymorphisms on the Risk of Duodenal Ulcer. In Journal of epidemiology, 31, 12-20. doi:10.2188/jea.JE20190184. https://pubmed.ncbi.nlm.nih.gov/31839644/