Liu Yongshun, Huang Wenpeng, Hsu Jessica C, Sun Zhaonan, Cai Weibo, Kang Lei
Department of Medical Imaging, Peking University First Hospital, Beijing 100034, China.
Department of Nuclear Medicine, Peking University First Hospital, Beijing 100034, China.
iScience. 2025 Sep 2;28(10):113491. doi: 10.1016/j.isci.2025.113491. eCollection 2025 Oct 17.
Claudin18.2 (CLDN18.2), a specific tight junction protein isoform, is minimally expressed in normal gastric mucosa but aberrantly overexpressed in various cancers. It plays a key role in regulating tumor cell differentiation, proliferation, and migration, making it an attractive therapeutic target, especially in gastric cancer. Moreover, molecular imaging techniques such as immuno-positron emission tomography, immuno-single photon emission computed tomography, and near-infrared fluorescence imaging enable non-invasive evaluation of CLDN18.2 expression, improving diagnosis and guiding personalized treatment. This review summarizes recent advances in CLDN18.2-targeted therapies and molecular imaging for cancer management. We outline the biomarker's biological functions and signaling pathways across cancers, highlighting the development of precision therapeutics. We also discuss applications and limitations of CLDN18.2-targeted theranostics in digestive malignancies and address clinical translation challenges and future directions.
紧密连接蛋白18.2（CLDN18.2）是一种特定的紧密连接蛋白异构体，在正常胃黏膜中表达极低，但在多种癌症中异常过表达。它在调节肿瘤细胞分化、增殖和迁移中起关键作用，使其成为一个有吸引力的治疗靶点，尤其是在胃癌中。此外，免疫正电子发射断层扫描、免疫单光子发射计算机断层扫描和近红外荧光成像等分子成像技术能够对CLDN18.2表达进行无创评估，改善诊断并指导个性化治疗。本综述总结了CLDN18.2靶向治疗和癌症管理分子成像的最新进展。我们概述了该生物标志物在各种癌症中的生物学功能和信号通路，强调了精准治疗的发展。我们还讨论了CLDN18.2靶向诊疗在消化系恶性肿瘤中的应用和局限性，并探讨了临床转化挑战和未来方向。
