Biomarkers

Could a Simple Blood Test Help Diagnose Mesothelioma…Earlier?

Despite advances in treatment options for malignant pleural mesothelioma, the median survival for patients remains 12 months.  Promising new treatments, such as targeted biologic therapies that can be taken orally, are currently being studied in clinical trials.  The hope is that targeted therapies will work more efficiently and effectively to eradicate the cancer and help prevent recurrence.  Researchers are also focusing on improving early disease detection and supporting individualized treatment strategies through the discovery of new biomarkers.

Dr. Harvey I. Pass, Chief of Thoracic Oncology at NYU Cancer Center and Chief of Thoracic Surgery ay NYU Langone Medical Center, sees the vast potential of blood tests to diagnose mesothelioma, particularly in earlier stages of the disease.  The blood tests could also be used to determine the best treatment options for particular patients based on specific characteristics of each individual’s disease state.

As a principal investigator for The North American Mesothelioma Consortium, one of the Biomarker Developmental Laboratories funded by the National Cancer Institute (NCI), Dr. Pass has devoted much of his research to identifying biomarkers in the blood that could lead to earlier mesothelioma diagnosis, as well as more personalized treatment protocols.  He and his team hope to identify blood-based biomarkers that can improve ease-of-use and predictive accuracy for diagnosing and treating mesothelioma and other lung cancers.

But before we discuss the role of biomarkers in mesothelioma diagnosis and treatment, let’s first understand what makes mesothelioma such a challenging disease to diagnose and treat.

Mesothelioma Symptoms Typically Manifest Later in Disease Progression

Seventy-five percent of mesothelioma cases are linked to asbestos exposure.

The time between first exposure and diagnosis is typically 20 to 50 years.  At the point when most mesotheliomas are discovered, patients are already in the later stages of the disease and manifesting symptoms such as chest pain, coughing and shortness of breath.

When malignant plural mesothelioma patients start to show symptoms such as difficulty breathing, the disease is typically already in Stage III or IV. At that point, the disease has likely spread to other areas of the body such as the lymph nodes, diaphragm muscle, heart tissue and other areas.  Patients may show mild symptoms at Stage II, but they are usually difficult to link to mesothelioma and may even be mistaken for the flu.  Unfortunately, the typical prognosis for patients – especially over the age of 45 – is relatively low.

Not surprisingly, the earlier mesothelioma can be detected, the better the outlook for patients.  Unfortunately, less than ten percent of mesotheliomas are found in Phase I of the disease.

Early Mesothelioma Diagnosis Remains a Challenge

Early diagnosis of malignant plural mesothelioma remains challenging particularly because patients do not typically show specific symptoms in the early stages of the disease.

For people who have knowingly been exposed to asbestos, some doctors recommend regular x-rays or CT scans to look for changes in the lungs that could be indicative of mesothelioma or lung cancer.  However, it is not clear how effective imaging is at detecting of these diseases, nor is ongoing imaging a cost-effective, long-term solution.

Doctors also use biopsies for diagnosing malignant plural mesothelioma; however, biopsies are invasive and usually performed in the later stages of the disease after the patient has already begun to show symptoms.

Researchers believe they can find less invasive, more personalized and more cost-effective methods for diagnosing mesothelioma earlier and more precisely.  Some current research is seeking to identify diagnosticbiomarkers in blood or fluid that can provide information about whether someone who has been exposed to asbestos has developed mesothelioma.

What is a Biomarker?

Generally speaking, in medical practice, a biomarker is something in the body or related to the body that can be objectively measured and evaluated to provide information about a patient’s biological processes.  Some of the most widely used biomarkers include pulse and blood pressure measurements, as well as blood tests.

As they relate to mesothelioma, biomarkers typically refer to levels of particular proteins in tissue, fluid or blood that are expressed by specific genes.  Elevated or low levels of certain biomarkers could indicate the presence of mesothelioma.

Current Mesothelioma Biomarkers Lack Sensitivity and Specificity

Biomarkersare currently used in the diagnosis and treatment of mesothelioma but, presently, they are inadequate at consistently and accurately identifying mesothelioma cancer.For example, a protein called mesothelin is a highly-studied biomarker used in the diagnosis of mesothelioma and other cancers.  Elevated levels of mesothelin indicate the presence of cancer. But the test for mesothelin has low sensitivity, which means that it is unable to detect mesothelioma in some people who have the disease.

Similarly, other biomarkers lack specificity, which means that they are unable to consistently distinguish between people who do have mesothelioma and those who do not, resulting in false-positives.

Research Reveals Promising Biomarkers for Mesothelioma

In the search for more sensitive and specific biomarkers that can help diagnose mesothelioma earlier and contribute tomore personalized treatment options, promising biomarkers continue to emerge.

Fibulin-3, which has been studied by Dr. Harvey Pass and his colleagues at New York University Langone Medical Center, is a biomarker found in blood plasma and lung fluid.  Their research conclusions, published in TheNew England Journal of Medicine,indicated a high predictive correlation between high fibulin-3 levels and the presence of malignant pleural mesothelioma.

Although further study is needed before definitive and actionable conclusions may be drawn, these findings hint at an early detection method that could distinguish between healthy people who have been exposed to asbestos and those who have developed mesothelioma.  An added benefit of this type of biomarker is that the information can be gleaned from a simple blood test.

Researchers in Japan have published positive findings in Journal of Clinical Gastroenterologyabout HMGB1, another diagnostic biomarker that can be measured by a blood test.  The team found that patients with diffuse malignant peritoneal mesothelioma had significantly higher levels of HMGB1 than those who had also been exposed to asbestos but did not develop the disease.

Not only are these promising new mesothelioma biomarkers potentially more sensitive and specific, they can also be measured through a simple blood test rather than an invasive tissue or fluid biopsy or expensive and unreliable imaging.

BiomarkersCan Help Identify Optimal Treatment Protocols for Specific Patients

Even if doctors are able to use blood-borne biomarkers to diagnose mesothelioma earlier, they still face the challenge of treating the disease.  Typically, radiation, chemotherapy and/or surgery are used to treat malignant plural mesothelioma. But the cancer is highly resistant to both radiation and chemotherapy.  In addition, surgery is highly-invasive and physically taxing and may not be appropriate for patients who are elderly or whose cancer has spread.

Currently, it is difficult to know in advance which patients will respond best to particular treatments or drugs.  Researchers hope that they will be able to identify biomarkers that will not only help with early diagnosis but will provide insight into which treatment options will be most effective for individual patients.

As researchers, such as those involved with the NCI’s Biomarker Developmental Laboratories, continue to identify cancer biomarkers, we can expect to see an increasing number of studies seeking to validate the specificity and sensitivity of promising biomarkers.  The studies will take time, but the promise of robust blood-borne biomarkers that will help doctors diagnose and treat mesothelioma appear to the on the horizon.

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