Integrated diagnostics, including immunohistochemistry, RNA in situ hybridization, and next-generation sequencing, are needed to accurately profile claudin expression for precision medicine.

Claudins maintain epithelial barrier function; their dysregulation disrupts signaling pathways like AKT and MAPK and shapes the tumor microenvironment, affecting immune infiltration and extracellular matrix dynamics.

Heterogeneity of claudin expression across cancers and within tumors poses a key challenge, underscoring the need for isoform-specific biomarker-driven patient selection and robust companion diagnostics.

Advances include structure-function studies of claudins, identification of claudin-specific antibodies and ADCs, and preclinical reports of claudin-targeted imaging and modulation of fibrosis/inflammation.

Therapies exploit claudin extracellular domains for targeted delivery while also exploring intracellular targeting to modulate downstream signaling and improve response durability.

Overexpression of claudins in solid tumors is linked to tumor growth, EMT, cancer stem cell traits, and drug resistance, making them central to cancer progression and treatment strategies.

Understanding resistance mechanisms—such as claudin isoform switching and junctional remodeling—is essential for designing combination strategies that sustain therapeutic efficacy.

Key mechanistic insights include how tight junction components interact with PDZ-domain proteins, regulate epithelial polarity, and influence signaling pathways and EMT.

Claudins influence tumor immunity, presenting potential synergy when combined with immune checkpoint inhibitors to enhance anti-tumor responses.

Targeting intracellular claudin pathways and protein interactions can complement extracellular antibody-based therapies, addressing extracellular heterogeneity with an additional modality.

Claudin proteins are emerging targets in cancer therapy, with their roles in tight junctions and epithelial barrier function across various cancers driving both tumor progression and potential treatment approaches.

The field is shifting from viewing claudins as mere barrier components to recognizing them as actionable targets for therapy and diagnostics, with several CLDNs such as CLDN18.2, CLDN1, and CLDN6 moving toward clinical development.