CLDN6 in cancer: Biology, clinical significance, and emerging therapeutic strategies.

Claudin-6 (CLDN6) is an essential component of tight junctions (TJs) with a characteristic oncofetal expression pattern, being largely absent in normal adult tissues but re-expressed in multiple malignancies. This tumor-restricted expression profile provides a potential therapeutic window for CLDN6-directed targeting. Increasing evidence indicates that CLDN6 participates in diverse aspects of tumor biology, including regulation of tumor growth, metastasis, metabolic reprogramming, immune microenvironment remodeling, and therapeutic resistance. Consequently, CLDN6 has emerged as both a cancer biomarker and a promising therapeutic target. Furthermore, we focused on the expression landscape and biological functions of CLDN6 across cancer types and discussed its clinical relevance in tumor progression and prognosis. We further highlighted recent advances in CLDN6-targeted therapeutic strategies, including monoclonal antibodies (mAbs), T cell-engaging antibodies (TCEs), antibody-drug conjugates (ADCs), and adoptive cell therapy (ACT). Collectively, these developments provide important insights into the translational potential of CLDN6 and support its continued exploration as a precision therapeutic target in CLDN6-positive cancers.