01. Mesothelioma Blood Test Overview
What Are Blood Tests for Mesothelioma?
Blood tests for mesothelioma check for signs suggesting a patient may have mesothelioma. These tests measure specific substances called biomarkers. Biomarker testing can help doctors rule out or confirm potential diagnoses, including mesothelioma. Doctors may use blood tests with other tests, such as imaging scans and biopsies, to diagnose mesothelioma.
The MESOMARK® assay is the only approved mesothelioma blood test in the United States. It measures biomarkers associated with mesothelioma.
Some cancers have well-established, standard biomarkers. These biomarkers may help identify early cancer cases. Other biomarkers may signal higher than normal risks for developing a certain cancer.
Blood tests that find biomarkers for elevated risk or early cancer may impact prognosis. In mesothelioma, earlier diagnosis is linked to improved life expectancy. As such, blood tests for mesothelioma biomarkers could theoretically improve a patient’s mesothelioma prognosis.
Experts have identified biomarkers for mesothelioma diagnosis. But these biomarkers have not yet proven useful for early diagnosis. Similarly, mesothelioma research has not yet found biomarkers for elevated risk of this rare cancer. Doctors continue to search for good mesothelioma biomarkers.
What Makes a Good Mesothelioma Biomarker?
In general, good biomarkers have a few important qualities:
- The biomarker is in an easy-to-measure location, such as blood or saliva.
- The biomarker is specific. It is not present in patients who do not have the condition it tests for.
- The biomarker is sensitive. It is not absent in patients who do have the condition it tests for.
For mesothelioma, a good biomarker might be a protein with the following properties:
- Healthy cells do not make the protein, or they make very little of it.
- Mesothelioma cells make the protein.
- The protein is found and easily measurable in blood.
Such a protein might help doctors identify earlier cases of mesothelioma.
Currently, biomarker blood testing alone is not sufficient to diagnose mesothelioma. But it can trigger more robust diagnostic testing, such as a biopsy. With biopsy results, doctors may be able to confirm or rule out a mesothelioma diagnosis.
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02. How Blood Tests Find Mesothelioma
How Do Blood Tests Detect Mesothelioma?
Mesothelioma blood tests detect substances associated with the cancer. They do not detect tumor cells directly. Finding a mesothelioma biomarker may mean a patient has cancer cells in their body.
As of May 2022, there is only one approved blood test for mesothelioma. The MESOMARK assay gained U.S. Food and Drug Administration (FDA) approval in 2007. It does not detect or diagnose mesothelioma. MESOMARK measures mesothelioma biomarkers. This test can help doctors monitor certain patients after a mesothelioma diagnosis.
Blood test screening alone cannot diagnose mesothelioma. But blood test results may help doctors order additional tests that can diagnose it. Doctors generally need a tissue biopsy and related testing to confirm a mesothelioma diagnosis.
Researchers are looking for ways to improve known biomarkers. They are also searching for new biomarkers. Their work may one day lead to improved mesothelioma diagnostic tests.
Can Blood Tests Detect Asbestos Exposure?
A blood test capable of detecting asbestos exposure might be useful. Asbestos fibers cause mesothelioma. But some people may not know they have encountered asbestos. A biomarker reflective of asbestos exposure could help such individuals.
Scientists could use such a biomarker to create a blood test for asbestos exposure. A positive asbestos blood test could signal the need to monitor for mesothelioma symptoms. This could allow earlier detection of mesothelioma, potentially improving prognosis.
Researchers have not yet validated biomarkers for this purpose. As such, no asbestos blood test truly exists today. However, studies have identified potential asbestos biomarkers.
If validated in the future, these biomarkers could inform people of unknown asbestos exposure. This might help them secure appropriate testing if they ever develop mesothelioma symptoms.
03. Biomarkers for Mesothelioma
Mesothelioma biomarkers are substances that may indicate the presence of mesothelioma. Tests may detect biomarkers in blood or biopsy tissue samples. Doctors may use mesothelioma biomarker tests alongside tests for other conditions. This provides information to help rule out other conditions or confirm mesothelioma.
Tissue Biomarkers Used in Mesothelioma Diagnosis
Supporting a Mesothelioma Diagnosis
- Keratins 5 and 6
Not Supporting a Mesothelioma Diagnosis
Researchers have investigated many potential mesothelioma biomarkers. Some of these may have the capacity to become diagnostic or monitoring biomarkers. Potentially useful mesothelioma biomarkers include fibulin-3, MPF/n-ERC mesothelin and SMRPs.
Biomarkers With Potential for Mesothelioma Diagnosis
Fibulin-3 is a special type of protein called a glycoprotein. Research indicates pleural mesothelioma patients produce abnormally high levels of fibulin-3. It may be detectable in blood or biopsy fluid.
Fibulin-3 testing may distinguish between mesothelioma and other cancers. It may also distinguish between mesothelioma and some benign conditions.
Fibulin-3 research is ongoing.
Megakaryocyte potentiation factor (MPF) is a special type of protein called a glycoprotein. It also goes by the name n-ERC mesothelin.
MPF blood testing found the protein in mesothelioma patients. Doctors did not find MPF in blood from healthy volunteers.
Studies show MPF levels may distinguish healthy individuals from those with mesothelioma. MPF may also discern between mesothelioma and benign asbestos conditions.
Soluble mesothelin-related peptides (SMRPs) are detectable in blood. SMRPs are pieces of a protein called mesothelin. SMRPs can break apart from mesothelin and circulate in a patient’s blood.
MPF is a specific form of SMRP. SMRP tests often measure various SMRPs, including MPF.
Mesothelioma patients have higher SMRP levels than healthy patients. SMRPs form the basis of the MESOMARK blood test. They may aid in monitoring mesothelioma patients.
Biomarkers for Detecting Asbestos Exposure
The development of an asbestos blood test might enable early mesothelioma detection. However, such a test would require good asbestos biomarkers. Researchers have not yet settled on reliable biomarkers for asbestos exposure. But a few have shown promise. Potential biomarkers for detecting asbestos exposure include:
- 8OHdG: 8-hydroxy-2′-deoxyguanosine (8OHdG) is a molecule associated with asbestos. When cells undergo asbestos damage, they produce 8OHdG. Research shows people exposed to asbestos have higher than normal 8OHdG levels.
- HMGB1: High mobility group box 1 protein (HMGB1) is a protein affected by asbestos. Research indicates people exposed to asbestos have higher than normal HMGB1 levels.
- SMRPs: Soluble mesothelin-related peptides (SMRPs) are broken pieces of mesothelin protein. SMRP testing has differentiated between people exposed to asbestos and those with no exposure.
If verified, these biomarkers could have a substantial impact on mesothelioma prognosis. They might someday enable earlier detection of this cancer. Patients diagnosed in stage 1 live nearly twice as long as those diagnosed in stage 4. As such, early detection through asbestos biomarkers might positively impact many mesothelioma patients.
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The MESOMARK Blood Test for Mesothelioma
The MESOMARK assay is the only FDA-approved blood test for mesothelioma. Doctors can use it to monitor mesothelioma patients. It may also have the potential to detect mesothelioma earlier than current methods. However, MESOMARK does not have approval for mesothelioma diagnosis.
An assay is a scientific test. It generally measures the amount of a substance of interest in a sample.
The MESOMARK assay measures SMRPs in human serum, which is a component of blood. SMRPs are small pieces of a protein called mesothelin. Healthy cells and mesothelioma cells both make mesothelin. But mesothelioma cells make more mesothelin than normal.
Pieces of mesothelin can break off, creating SMRPs. SMRPs can then enter the bloodstream. SMRP blood testing shows mesothelioma patients have higher SMRP levels than healthy individuals.
A high SMRP level might indicate a patient has mesothelioma. But MESOMARK does not have approval to diagnose mesothelioma. The MESOMARK label says the test can help monitor patients with epithelioid mesothelioma. It may also assist in monitoring biphasic mesothelioma. MESOMARK is not intended for use in sarcomatoid mesothelioma patients.
The MESOMARK Testing Process
The MESOMARK assay follows a process like several other blood tests. The MESOMARK assay process may include the following steps:
- A healthcare professional collects a blood sample.
- The sample undergoes processing to prepare it for testing.
- The test operator combines the prepared sample with testing materials. These include special proteins (antibodies) that stick to SMRPs.
- After some time, more testing materials are added to the sample. These materials create a light when they bump into the SMRP antibodies.
- A machine measures the light created by the test sample.
- The machine determines the amount of SMRPs in the patient’s sample.
Generally, a doctor or pathologist examines the test results and discusses them with the patient. This discussion is important, as the test results alone may be difficult to interpret.
Mesothelioma Blood Test Technology Spotlight: ELISA Assays
The MESOMARK test is an enzyme-linked immunosorbent assay (ELISA). ELISA kits are common in many areas of healthcare and diagnostic research. They use special molecules that produce light in response to a target molecule. The amount of light produced corresponds to the amount of target molecule present.
In the MESOMARK assay, blue light corresponds to the presence of SMRPs. The more blue light a test sample produces, the higher its level of SMRPs.
Could MESOMARK SMRP Blood Testing Detect Mesothelioma Early?
According to some researchers, SMRP blood testing can do more than monitor mesothelioma. Some say SMRP testing has potential for detecting mesothelioma in high-risk, asbestos-exposed individuals. Individuals who have held asbestos-related jobs may fall into this category.
Past SMRP studies may contribute to the researchers’ opinion on its potential. One long-term study took multiple SMRP readings over time. Tests showed elevated SMRP levels in patients who later developed mesothelioma. The elevated SMRP levels appeared one to five years before mesothelioma diagnosis.
In the same study, some asbestos-exposed people had consistently normal SMRP levels. At last follow-up, none of those patients had developed mesothelioma. The authors said SMRP testing might prove helpful in screening for early evidence of mesothelioma.
It is unclear whether mesothelioma doctors currently use MESOMARK to monitor SMRP changes over time. In any case, SMRP research continues. It may one day result in a blood test for early detection of mesothelioma.
05. Biomarker Research for Mesothelioma
Mesothelioma Biomarker Research
Mesothelioma research has impacted both diagnosis and treatment already. Investigation into mesothelioma biomarkers involves multiple aspects of the disease.
One area of research applies the science of biomarkers to mesothelioma treatment. A mesothelioma biomarker is present or plentiful in mesothelioma cells. As such, it could be called a mesothelioma tumor marker. With the right technology, a good mesothelioma biomarker could act as a homing beacon. It could help treatments target mesothelioma cancer cells.
Researchers have applied this line of thinking to recently developed immunotherapy. Scientists engineered cancer-killing immune cells to target mesothelin. This means the immune cells essentially targeted mesothelioma tumors. Compared to earlier treatments, patients in this study lived more than one year longer than average.
Study Spotlight: Mesothelioma Biomarker-Targeted CAR T Cells
A recent clinical trial used biomarker science to improve pleural mesothelioma treatment. Study patients had received at least one form of treatment before enrolling. Researchers treated these patients with two immunotherapies:
- Mesothelin-targeted CAR T cells: Scientists took a sample of the patient’s own immune cells. The cells were reprogrammed to fight mesothelioma by targeting mesothelin. The reprogrammed cells are called CAR T cells. After reprogramming, a healthcare provider gave the CAR T cells back to the patient.
- Pembrolizumab (Keytruda®): Pembrolizumab falls into the category of checkpoint inhibitor drugs. It interferes with an immune checkpoint that may stop immune cells from fighting cancer. Blocking this checkpoint may let immune cells attack tumors.
Study patients had a median survival of 23.9 months. This marks a substantial improvement versus prior studies of second-line treatment. It also shows the survival benefit of multimodal mesothelioma treatment, or combining two or more therapies.
Breath Testing for Mesothelioma
Researchers have studied compounds in exhaled air for potential use in mesothelioma diagnosis. Exhaled air has at least one advantage over other diagnostic materials. Doctors can easily collect exhaled breath from patients. Thus, a breath test for mesothelioma might improve the ease of diagnosis.
Scientists have worked toward establishing a profile of breath biomarkers useful for mesothelioma. But the science in this area is still young. Researchers say this technology holds promise but needs larger studies.
Breath testing for mesothelioma is not yet a reality for patients, but the possibility remains. Mesothelioma clinical trials may help bring this technology from the benchtop to the clinic. Such progress may improve the rate of early mesothelioma detection.
Other Research-Phase Mesothelioma Biomarkers and Tests
Scientists have investigated several other biomarkers for mesothelioma. Some have shown promise in early research, but their true potential is still unknown.
Calretinin is a protein found on the outside of cells. Mesothelioma cells make high levels of calretinin. Mesothelioma patients may have higher than normal levels of calretinin in their blood. It may someday be useful in a mesothelioma blood test.
Estrogen Receptor Beta
Estrogen receptor beta (ERβ) is a protein with many different functions. Researchers claim it could be useful as a prognostic marker for mesothelioma. In one study, patients with higher levels of ERβ had better survival.
Epidermal Growth Factor Receptor (EGFR)
Epidermal growth factor receptor (EGFR) is a protein that sticks up from the outside of a cell. It may have use as a prognostic marker for mesothelioma. In one study, higher levels of EGFR seemed to negatively affect prognosis.
Osteopontin is a protein made in high quantities by some tumors. Lung cancer, breast cancer and colon cancer cells make a lot of osteopontin. It has shown some promise in distinguishing mesothelioma from benign respiratory conditions. An osteopontin blood test for mesothelioma may not be around the corner. Experts say osteopontin lacks validation testing that might enable its use as a diagnostic tool.
SOMAscan® for Mesothelioma
The SOMAscan test uses a principle called proteomics. Proteomics studies proteins at a large scale, looking for patterns. These patterns might one day provide useful information for oncologists.
The SOMAscan test uses a proprietary tool called SOMAmer® technology. It measures more than 1,000 different proteins. In an early study, the SOMAscan test had promising diagnostic accuracy for mesothelioma. However, the test has not yet gained FDA approval.
The Future of Mesothelioma Biomarker Research
Scientists have identified multiple potential biomarkers for mesothelioma. Some have potential to identify past asbestos exposure. Others may facilitate diagnosis of mesothelioma cancer.
Biomarkers already play an important role in diagnostic testing for mesothelioma. But current standard tests involve biopsy tissue samples rather than blood. Further research may someday make mesothelioma blood tests a more integral part of this process.