PSCA, short for Prostate Stem Cell Antigen, is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein. It has diverse functions in different tissues, such as playing an inhibitory role in cell proliferation as well as a tumor-inducing role. PSCA is involved in the p38/NF-κB/IL-6 signaling pathway, positively regulating IL-6 secretion in prostate cancer cells [2,5].

Variants in the PSCA gene have been associated with the risk of multiple cancers and non-neoplastic diseases. For example, six variants were significantly associated with an increased or reduced risk of three cancers and three non-neoplastic diseases. Cumulative evidence shows strong associations between certain variants like rs2294008, rs2976392, etc., and gastric cancer, bladder cancer, gastritis, duodenal ulcer, and gastric ulcer [3]. In addition, the PSCA rs2294008 T polymorphism is related to increased cancer susceptibility, especially for gastric and bladder cancers [6].

CAR-T cell therapies targeting PSCA are being explored in metastatic castration-resistant prostate cancer, metastatic pancreatic cancer, and gastric cancer. Some clinical trials show certain efficacy, such as prostate-specific antigen declines and radiographic improvements in prostate cancer patients, and anti-tumor cytotoxicity in vitro and in vivo in gastric cancer models [1,4,7].

In conclusion, PSCA is a cell-surface protein with complex functions, and its gene variants are associated with cancer and non-neoplastic disease risks. The use of PSCA as a therapeutic target in CAR-T cell therapies shows potential in treating various cancers. The study of PSCA through genetic models helps in understanding disease pathogenesis and developing new treatment strategies.