Claudins: from gatekeepers of epithelial integrity to potential targets in hepato-pancreato-biliary cancers

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Hyein Jeon1,2, Michelle Sterpi1,2, Christiana Mo1,2

  • 1Department of Medical Oncology, Albert Einstein College of Medicine, Bronx, NY, United States.

Frontiers in Oncology
|October 11, 2024
PubMed

Insights

Claudins are key proteins for cell junctions. Their abnormal expression links to cancer, and targeting them shows promise for treating hepato-pancreato-biliary malignancies, though challenges persist.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Biology

Background:

  • Claudins are transmembrane proteins crucial for tight junction integrity in epithelia and endothelia.
  • Altered claudin expression is implicated in various cancers, potentially driving tumor invasion and metastasis.
  • Hepato-pancreato-biliary (HPB) malignancies represent a significant area of unmet need.

Purpose of the Study:

  • To provide a comprehensive review of claudin functions, expression patterns, and roles in cancer.
  • To focus on the specific involvement of claudins in hepato-pancreato-biliary malignancies.
  • To explore the potential of claudins as therapeutic targets and review current targeted therapies.

Main Methods:

  • Literature review of claudin research, focusing on expression, cancer biology, and therapeutic strategies.
  • Analysis of pre-clinical and clinical data for claudin-targeted therapies.
  • Examination of challenges and future directions in claudin-targeted cancer treatment.

Main Results:

  • Claudins play multifaceted roles in cellular processes, including development, differentiation, and apoptosis.
  • Abnormal claudin expression is a hallmark of many cancers, impacting tissue architecture and promoting malignancy.
  • Current claudin-targeted therapies (e.g., monoclonal antibodies, ADCs, BiTEs, CAR-T) demonstrate promising efficacy in HPB cancers.

Conclusions:

  • Claudins are critical regulators of cellular integrity and are significantly dysregulated in cancer.
  • Targeting claudins offers a promising therapeutic avenue, particularly for difficult-to-treat HPB cancers.
  • Overcoming challenges related to claudin structural similarities and functional overlap is essential for optimizing targeted therapies.
Keywords:
bile duct cancercancer therapeuticsclaudinsgallbladder cancerhepatocellular carcinomapancreatic cancertargeted therapy

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