Claudin proteins as emerging therapeutic targets for solid tumours

Area of Science:

• Oncology
• Molecular Biology
• Cancer Therapeutics

Background:

• Claudins (CLDNs) are transmembrane proteins crucial for epithelial cell polarity and tight junction integrity.
• Overexpression of CLDNs is common in solid tumors, correlating with subtype, grade, and prognosis.
• Dysregulated CLDN expression impacts tumor proliferation, metastasis, stemness, and therapeutic resistance.

Purpose of the Study:

• To review the functional role of CLDN biology in solid tumors.
• To summarize the clinical development of CLDN-targeted therapeutic approaches.
• To discuss opportunities for biomarker-enriched patient selection in CLDN-targeted therapies.

Main Methods:

• Literature review of CLDN function in cancer.
• Summary of clinical trials and approved therapies targeting CLDNs.
• Analysis of CLDNs as biomarkers for patient selection.

Main Results:

• CLDNs are frequently overexpressed in solid tumors and contribute to oncogenic signaling.
• CLDN-directed therapies, including a monoclonal antibody targeting CLDN18.2, have shown clinical efficacy.
• Various CLDN-targeting strategies, such as antibody-drug conjugates and CAR T-cells, are under development.

Conclusions:

• CLDNs represent attractive therapeutic targets in oncology due to their overexpression and functional roles in cancer.
• CLDN-directed approaches, including biomarker selection, are emerging as a precision oncology strategy for multiple solid tumors.
• Targeting CLDNs offers a validated and evolving therapeutic avenue with significant potential in cancer treatment.