Mesothelin Expression in Mesothelioma

What Is Mesothelin?

Mesothelin is a protein found on the surface of mesothelial cells. Researchers suspect that the mesothelin protein plays a role in cell adhesion. This process allows cells to interact with and attach to neighboring cells.

Studies suggest that an interaction between mesothelin and a protein called MUC16 or CA125 may promote the spread of peritoneal mesothelioma tumors by cell adhesion.

Mesothelin can be over-expressed (over-produced) by several cancers, including malignant mesothelioma, ovarian cancer and pancreatic adenocarcinoma.

This factor makes mesothelin a good candidate as a tumor marker to diagnose and track mesothelioma. It’s also a good target for anti-cancer therapy.

Tracking Mesothelin Throughout Treatment

As mesothelioma tumors grow, they produce more mesothelin. When tumors shrink, they produce less mesothelin. Measuring mesothelin allows doctors to monitor the growth of mesothelioma and its response to treatment.

A 2006 study published in Clinical Cancer Research reported a 71% decrease in mesothelin levels the day after cytoreductive surgery among peritoneal mesothelioma patients. Mesothelin became undetectable by the seventh day after surgery. This research suggests that mesothelin can help doctors monitor a patient’s response to treatment.

The big hope with mesothelin is that it will prove an effective target for anti-cancer therapy among people with mesothelioma.

Mesothelin Expression in Mesothelioma

Healthy mesothelial cells express mesothelin. That expression increases when the cells become cancerous. Mesothelin expression is high in epithelial mesothelioma tumors but not in sarcomatoid tumors. This limitation means mesothelin does not help diagnose, monitor or treat sarcomatoid mesothelioma.

Doctors have tried to develop a mesothelin cancer test, but it hasn’t proven successful as a diagnostic tool. However, it is helpful when combined with other diagnostic tests to confirm a mesothelioma diagnosis.

Doctors use a mesothelin ELISA test to measure mesothelin levels in a person’s blood. ELISA stands for enzyme-linked immunosorbent assay, and it uses antibodies and color change to identify substances.

Mesothelin Tests

These tests help doctors diagnose cancer and monitor its growth or response to treatment. Several blood tests measure mesothelin through soluble mesothelin-related peptides (SMRP), which are soluble molecules related to the mesothelin family of proteins.

MESOMARK and the N-ERC/mesothelin test are the most well-known tests. In 2007, the FDA approved MESOMARK as a tool to monitor mesothelioma but not a diagnostic tool.

MESOMARK and N-ERC/mesothelin cannot diagnose mesothelioma on their own. However, researchers are hopeful that combining a mesothelin test with tests that measure other biomarkers, such as calretinin, will improve mesothelioma detection. Another mesothelin blood test is under review at the University of Bristol in the United Kingdom.

What Drugs Target Mesothelin?

Primary drugs that target mesothelin are part of a class of drugs called antibodies. The immunotherapy drug Amatuximab (MORab-009) targets mesothelin.

The immune system creates antibodies, proteins that hunt down things that cause harm, such as viruses, bacteria and cancer cells. These harmful agents have proteins called antigens that antibodies attach to, like a lock and key.

Mesothelin is an antigen, and the drugs that target it are antibodies.

Approximately 40% of mesothelioma patients’ immune systems generate anti-mesothelin antibodies. They attach to and attack mesothelin-bearing cells.

Researchers are working to identify anti-mesothelin antibodies to use as anti-cancer therapies. They have identified several and tested them in clinical trials without significant success.

Other types of anti-mesothelin drugs include CRS-207, which is a cancer vaccine that uses a modified form of the Listeria bacterium to target mesothelin. A person’s own immune cells, called CAR T cells, and the microRNA molecule miR-21-5p also target mesothelin.

Mesothelin exists in both healthy and cancerous mesothelial cells, making it tricky to use it as a therapeutic target.

Mesothelin Antibody Research

There is a lot of research on anti-mesothelin antibodies. No available options have proven effective enough to be approved by the U.S. Food and Drug Administration (FDA).

But some of them have helped a handful of people with mesothelioma far outlive their prognosis.

For example, Andy Ashcroft lived for years with stage 4 pleural mesothelioma thanks to joining a clinical trial that tested Amatuximab, an anti-mesothelin antibody.

Ashcroft was among the few mesothelioma participants who responded to the drug. The trial ended because so few mesothelioma patients responded the way Ashcroft did.

Researchers are working on finding new anti-cancer agents that may one day work as an anti-cancer therapy for mesothelioma. A 2017 study identified a molecule called miR-21-5p that may block mesothelioma from spreading by targeting mesothelin.

A 2015 study in the journal Nature identified new antibodies, called YP218 and YP223, that target mesothelin. Extensive research is necessary to determine whether these new antibodies will prove successful.

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