AACR 2023: Study Identifies Genetic Marker in Cholangiocarcinoma

By: Joshua D. Madera, MS
Posted: Friday, April 28, 2023

The transmembrane protein claudin-1 (CLDN1) was found to play a critical functional role in the pathogenesis of cholangiocarcinoma, according to a presentation given at the American Association for Cancer Research (AACR) Annual Meeting 2023 (Abstract LB012/4). Therefore, the development of monoclonal antibodies directed against CLDN1 for the treatment of cholangiocarcinoma may be an effective therapeutic strategy, explained Emilie Crouchet, PhD, of the Université de Strasbourg, France, and colleagues.

Tissue samples from patients with cholangiocarcinoma were collected to assess the therapeutic impact of drugs targeting CLDN1. In addition, cell line–derived xenografts from mice and patient-derived xenografts from patients with cholangiocarcinoma were exposed to monoclonal antibodies against CLDN1 to quantify its genetic expression. To investigate tumor signaling and cell fate, RNA sequencing was performed.

The analyses revealed a significant increase in CLDN1 expression in patients with cholangiocarcinoma. CLDN1 was identified as a therapeutic target for patients with cholangiocarcinoma, given the increased expression of the cell cycle, interferon response signature, and epithelial-mesenchymal transition found in the tumor microenvironment. Moreover, in vivo antitumoral effects were revealed across cell line–derived xenografts and patient-derived xenografts models through monoclonal antibody targeting. These effects were pronounced in both intrahepatic and extrahepatic cases of cholangiocarcinoma. Furthermore, monoclonal antibodies targeted against CLDN1 led to a suppression of the cellular invasion and migration of tumor cells. Specifically, suppression of the Notch1, Src, and Hippo-YAP signaling pathways was revealed with the use of monoclonal antibodies against CLDN1.

Disclosure: For full disclosures of the study authors, visit abstractsonline.com.

AACR Annual Meeting 2023

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