Mesothelin Protein Expression In Mesothelioma

Mesothelin is a protein that is created by the cells that line the pleura, pericardium, and peritoneum. These cells are called mesothelial cells and when they become cancerous they begin to produce mesothelin at higher rates than healthy cells.

Malignant mesothelioma, in addition to some other cancers like ovarian and pancreatic, produces mesothelin over and above the expected levels. This overexpression makes the protein an ideal candidate for a biomarker to help diagnose and treat mesothelioma. Mesothelin can also act as a target for some anti-cancer treatments.

What Is Mesothelin?

Those cells are called mesothelial cells, and they are suspected to play a role in the ability of cells to adhere to other nearby cells and interact with them. Some studies show that there may be a link between mesothelin and another protein called CA125 that may help peritoneal mesothelioma tumors spread.

The drawback to using mesothelin expression is that the over-expression only occurs in epithelial mesothelioma tumors, not sarcomatoid tumors. So as a result, mesothelin is not helpful or effective at the diagnosis, monitoring, or treatment of sarcomatoid tumors or biphasic tumors. There have been attempts to develop a cancer test based on mesothelin alone but it has not been found reliable or successful as a standalone diagnostic tool.

Mesothelin Tests

There are several blood tests that can be used to help build a diagnosis for mesothelioma, or that can be used to monitor the growth of tumors or their response to treatment. Two of the most well-known are the Mesomark assay and the N-ERC/mesothelin test. 

Mesothelin-Targeting Drugs

They are proteins that hunt down and destroy foreign or harmful bodies, like viruses, bacteria, and even cancer. A portion of patients generate anti-mesothelin antibodies that attack cells producing mesothelin and researchers have been working to identify additional mesothelin-targeting antibodies to use as cancer-fighting therapies.

Currently, there are several antibody drugs that target mesothelin, including:

• SS1P
• LMB-100/SEL-403
• Amatuximab
• Anetumab Ravtansine

Additional drugs that have shown promising interaction with mesothelin include:

• CRS-207, a potential cancer vaccine that uses Listeria to target mesothelin
• miR-21-5p is a microRNA molecule that targets mesothelin
• Immune cells from the patient modified to target mesothelin 

Ongoing Antibody Research

Research is continually advancing and working to find new and more effective antibodies for fighting mesothelioma. While none have yet been given FDA approval, they have helped some patients well outlive the original prognosis from their mesothelioma diagnosis. Some potential treatments may even allow those with stage 4 pleural mesothelioma to live for several years beyond the initial projections.