Journal: Nature reviews. Cancer
This review article focuses on claudins (CLDNs) as both key regulators of tumour biology and emerging therapeutic targets in solid malignancies.
Key points:
- Biology and tumour roles:
- Claudins are tight junction transmembrane proteins essential for epithelial polarity and barrier integrity in normal tissue.
- In solid tumours, claudins are frequently overexpressed, with expression patterns that correlate with tumour subtype, grade and prognosis.
- Dysregulated claudin expression affects multiple hallmarks of cancer, including:
- Oncogenic signalling and proliferation
- Epithelial–mesenchymal transition (EMT) and acquisition of stemness features
- Fibrosis and tumour microenvironment remodeling
- Immune modulation
- Therapeutic resistance
- Rationale for targeting:
- Their frequent overexpression and accessible cell-surface localization make claudins attractive for targeted therapies and drug delivery.
- Surface expression can be exploited to selectively direct therapeutics into claudin-positive tumours while sparing most normal tissues.
- Therapeutic strategies:
- A monoclonal antibody against CLDN18.2 has achieved regulatory approval, clinically validating claudin-directed therapy.
- Additional approaches under development for various claudin family members include:
- Antibody–drug conjugates
- Bispecific and trispecific antibodies
- CAR T-cell therapies
- Beyond surface targeting, strategies aimed at intracellular claudin domains or downstream signalling pathways are being explored to disrupt claudin-driven oncogenic functions.
- Precision oncology implications:
- The review emphasizes claudin-directed therapy as a precision oncology strategy applicable across multiple solid tumours.
- It highlights the need for biomarker-enriched patient selection, using claudin expression patterns to identify patients most likely to benefit.
Overall, the article synthesizes current knowledge of claudin biology in solid tumours, outlines the therapeutic landscape, and underscores the translational potential of claudin targeting for tailored cancer treatment.