Mesothelioma Biomarkers

Mesothelioma is a rare cancer that is difficult to diagnose and treat, and research is still ongoing to find new treatment options for patients. One of these new areas of study involves biomarkers. Biomarkers are proteins found in or on the body’s cells. Researchers have found that certain biomarkers are present in the blood when a disease is present in the body.
While biomarkers cannot yet be used to accurately diagnose mesothelioma, they may be used to tell doctors and researchers if the disease is responding to treatment. Researchers are hopeful that less invasive and more effective methods of diagnosing and treating mesothelioma can be based on biomarker research.
Different biomarkers are present in the body depending on the stage of the disease. Doctors hypothesize that mesothelioma can be tracked from its beginnings (exposure to asbestos) to the final stages of the tumor. Groups of biomarkers at various stages are used by scientists for different applications.

Biomarkers of Exposure

When a person is exposed to asbestos and the fibers enter the body, damage already begins to occur. The byproducts of this process can be used to detect the beginning changes of cancer cells. Biomarkers of exposure are present in the body after asbestos is inhaled. Doctors can monitor these biomarkers to potentially track the progression of disease.

8OHdG

8OHdG is a biomarker for oxidation (cellular damage) and is often found in the body during the early stages of cancerous cell development. Elevated levels of 8OHdG have been found in people occupationally exposed to asbestos. It has also been linked to asbestosis.

• This is a clear marker of asbestos exposure.
• It cannot distinguish between an individual exposed to asbestos with mesothelioma or without mesothelioma.

Biomarkers of Diagnosis

Biomarkers that may help diagnose mesothelioma earlier are the most crucial for mesothelioma patients since an earlier diagnosis means more treatment options and possibly a greater chance of survival. Unfortunately, current studies have yet to find a biomarker that has the right sensitivity and accuracy to replace a biopsy as the preferred method of diagnosis.
Doctors find that these biomarkers are also useful for measuring a patient’s response to treatment.

Osteopontin (OPN)

Elevated levels of OPN have been found in patients with mesothelioma, but they have also been found in a number of other cancers.

• It shows potential for use as a way of assessing a patient’s response to treatment.
• This biomarker is not specific or sensitive enough to detect mesothelioma.

Soluble Mesothelin-Related Peptides (SMRPs)

SMRPs are currently the most reliable biomarkers for mesothelioma. It has been found that patients with mesothelioma have elevated levels of SMRP in the blood. However, it is also present in patients with other cancers.

• Reliable for detecting epithelioid mesothelioma.
• It lacks specificity to detect mesothelioma. Also, it lacks sensitivity for detecting non-epithelial mesothelioma.

Prognostic Biomarkers

Prognostic biomarkers may be used to determine the aggressiveness of a particular mesothelioma and to track its development. This may help doctors more accurately predict someone's mesothelioma prognosis.

Platelet Derivative Growth Factor (PDGF)

In some studies, the levels of PDGF in a patient’s blood correlated to a higher or lower survival. Patients with a lower level survived on average six months longer than patients with high levels, but these results were not as accurate when adjusted for age, gender and platelet count.

Estrogen Receptor-β (ER-β)

Studies revealed that patients with higher levels of ER-β in pleural tissues survived longer than patients with low levels. ER- β is normally found in healthy pleural (lining of the lungs and chest cavity) tissue.

Epidermal Growth Factor Receptor (EGFR)

Like ER- β, the presence of EGFR in patients was related to longer survival. The absence of this receptor was also linked to other predictors of poor prognosis, such as chest pain and weight loss.

Applications of Biomarkers

Studies on biomarkers have led to potential applications in the treatment of mesothelioma. One example of this is the development of the Mesomark blood test. The test, which is available commercially, was approved by the FDA in 2007 to monitor the progression of mesothelioma that has already been diagnosed.
Mesomark detects the levels of the SMRP biomarker in the blood, and doctors can use this information to see if the disease is responding to treatment. When SMRP levels are low, this usually correlates to a shrinking tumor.
Another clinical study of mesothelin revealed that the binding of this protein with CA-125, another biomarker, may be a component in the metastasis of mesothelioma. Scientists created an antibody called MORAb-009 to stop the binding process. They also found that MORAb-009 can kill mesothelin-expressing cells. This discovery can lead to new treatments that may help stop tumor growth and metastasis.

Tumor Markers vs. Biomarkers

While the term tumor marker is often used interchangeably with biomarker, the definitions of these two terms are slightly different. Tumor markers are substances found in or expressed by the actual tumor. Biomarkers can be other physiological markers or substances expressed by the body that can indicate the presence of a tumor though not necessarily expressed by tumor cells. Another distinction between these two terms is that biomarkers can also apply to non-solid tumor cancers such as those found in blood cancer.
For example, scientists recently discovered a tumor marker expressed by pleural mesothelioma tumor cells called intelectin-1. This tumor marker is specifically expressed by epithelioid-type mesothelioma tumor cells. It has a specificity of 88 percent, which makes this marker a good candidate for detecting epithelioid mesothelioma.
Many researchers believe tumor markers aren't sensitive enough to be used for screening, yet one tumor marker, the prostate-specific antigen (PSA), has been used in the screening of prostate cancer among men for several years and has shown much success. However, an elevated PSA level does not necessarily indicate cancer, but does indicate the need for further testing.