Claudin May Be the Next Big Target in Pancreatic Cancer Treatment

Wungki Park, M.D.
Pancreatic adenocarcinoma is one of the hide-and-seek champions of the cancer world, great at evading attempts by the immune system to find it and stealthily sending its carcinoma cells to invade other parts of the body, often before the main tumor is even discovered.

While immunotherapy and other targeted treatments involving monoclonal antibodies have been successful in other cancers, pancreatic cancer has been notoriously tough to target because of a lack of suitable cell surface targets to which the antibodies can bind.

But a new target has been identified, and researchers are hopeful that an investigational drug that homes in on it may be an effective treatment for metastatic pancreatic cancer.

Taking Advantage of a New Target

Claudin proteins regulate paracellular barriers to control the flow of molecules between cells, acting like a glue between cells that holds them together. They are found in healthy intestinal systems, but a certain isoform—CLDN18.2—is highly expressed in cancers of the gastrointestinal tract.

In this form, the glue is weaker, which may contribute to metastasis, since it becomes easier for cancerous cells to detach from the primary tumor and disperse. But it could also help expose antibodies for monoclonal antibodies to bind to.

One such monoclonal antibody, zolbetuximab (IMAB362), has been developed to seek out CLDN18.2 on the surface of tumor cells and bind to it, identifying the cells for immune-mediated destruction.

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