While there is no cure yet, a lot of effort is going into finding better treatments.
Early diagnosis is currently the best way to improve survival rates for mesothelioma.
Several biomarker blood tests show promise in detecting mesothelioma early.
Emerging treatments such as immunotherapy offer our best opportunities to develop a cure.
Finding a cure to eliminate mesothelioma is an ongoing and challenging process. With later stages of the disease (e.g., stage 3 or 4), the length and likelihood of survival becomes lower. Mesothelioma that is confined to the site of origin and can be removed by surgery alone is associated with the best survival rates. Alternatively, mesothelioma that has spread outside of the site of origin and cannot be removed by surgery has the shortest survival time.
Because of this, researchers are currently focusing efforts on better ways to diagnose mesothelioma earlier, as well as find new treatment options. While a cure has not yet been found, survival has been slowly improving over time due to research advances.
History of Finding a Cure for Mesothelioma
Just a century ago, mesothelioma was an unknown disease. Since mesothelioma was discovered among industrial workers in the early to mid-1900s, physician-scientists have been carefully studying the disease in search of curative treatments.
The term mesothelioma first was used in 1920, and nearly four decades later the association was made between mesothelioma and asbestos exposure. Early on in the 1940s, mesothelioma was initially treated by removal of the entire lung and pleura through complex surgeries. The invasiveness of surgeries has decreased over the next several decades with the use of more advanced surgical techniques and lung-sparing procedures.
In addition to surgery, the use of radiation and systemic therapies (chemotherapy) were introduced in the early 2000s and continue to be used today. In 2004, a treatment breakthrough occurred when the United States Food and Drug Administration (FDA) approved the drug Alimta (pemetrexed) for use in combination with cisplatin for patients with malignant pleural mesothelioma. It was the first drug to receive FDA approval for mesothelioma, and the combination of pemetrexed and cisplatin is considered the gold standard chemotherapy for mesothelioma.
Clinical trials investigating the use of other novel treatment regimens for mesothelioma are ongoing at this time.
Challenges in Curing Mesothelioma
There are many hurdles to finding a cure for mesothelioma. Some of these challenges involve fighting the disease itself, while others are tied to detection and diagnosis before tumors become untreatable.
Traditional Diagnosis Improvements
A significant challenge in mesothelioma treatment is the inability to diagnose the disease at an early stage. This is often related to the fact that diagnosis requires distinguishing mesothelioma from other benign diseases of the lung lining, such as asbestosis or other inflammatory conditions.
Another difficulty in early diagnosis is that patients often do not develop symptoms until decades after they are exposed to asbestos, when the disease is at a more advanced stage. Because of this factor, the need for careful surveillance in high-risk individuals is critical. Limitations of surveillance with imaging tests and procedures (e.g., MRI or CT scan) is that the procedure is costly over time, and incidental findings on imaging may lead to unnecessary procedures for patients.
Early Detection through Biomarkers
Research has been conducted to identify a specialized characteristic, called a biomarker, to identify the disease at an early stage. While several biomarkers have been developed, no single one has been identified as the standard of care for mesothelioma surveillance. Mesomark, Osteopontin, N-ERC and miR-625-3p are examples of biomarkers that have been developed. While no marker has established superior sensitivity and specificity, the Mesomark assay is most commonly used. A brief description of each marker and any relevant research is below.
Biomarkers and How They Work
This assay (blood test) is the first biomarker test approved by the FDA. Approval was granted after several studies showed its usefulness in detecting a specific protein (soluble mesothelin-related protein, or SMRP) found in high concentrations in patients who have mesothelioma.
This test looks for a protein called osteopontin that has been found to have a high specificity, but a low sensitivity, for the disease. A 2014 study suggested that this test can be used to confirm a diagnosis, rather than to screen patients for the disease. It also suggested that higher levels of osteopontin may correlate to shorter survival times.
This blood test detects a protein called N-ERC/mesothelin that is present in high levels in patients with mesothelioma. It may be more accurate in detecting specific cell types of mesothelioma, such as epithelial mesothelioma. A 2014 study indicated favorable results; however, the study only looked at a small sample of patients. Further research is necessary to determine usefulness of this test.
This blood test measures the response of a molecule involved in gene regulation, known as miR-625-3p. An increased response in this molecule has been associated with the development of mesothelioma. A 2012 study determined that miR-625-3p is a novel diagnostic biomarker in mesothelioma. Additional studies are necessary to confirm the results.
More Effective Mesothelioma Treatments
Many researchers have devoted efforts to studying and testing novel treatment options for mesothelioma. New mesothelioma treatments are tested in clinical trials, which are conducted in phases from phase I to phase IV. Phase I trials are first-in-human studies, while phase IV trials involve drugs which have already been granted approval and are investigating additional information.
Clinical trials are closely monitored and regulated by several different groups. Enrollment in a clinical trial is voluntary and done though the National Comprehensive Cancer Network (NCCN). All clinical trials carried out within the United States must be registered with the National Institutes of Health (NIH) and can be found at ClinicalTrials.gov.
Specific types of mesothelioma treatment and trials are described briefly below.
This treatment involves the administration of a medication that “boosts” the individual’s natural immune system to fight off the cancer. It also offers a highly selective treatment approach and has minimal impact on normal tissues.
A drug that is currently FDA approved for skin and lung cancer called Keytruda (pembrolizumab) has shown to be safe and may be beneficial for patients with mesothelioma, according to early clinical trials. It is a special type of immunotherapy called a monoclonal antibody that targets a specific part of a cancer cell, called the programmed death-1 receptor (PD-1). Studies with Keytruda are currently in phase II.
Avastin® (bevacizumab) is another type of monoclonal antibody that has demonstrated survival benefit in clinical trials for patients with mesothelioma, when used in combination with Alimta® (pemetrexed) and cisplatin.
The p53 gene is involved in the prevention of tumor formation. Researchers have discovered that in some types of solid tumors, a defect or mutation in the p53 gene leads to the development of cancer. Whether activating a specific protein may either repair or kill damaged genes is currently being investigated with p53 restorative drugs. Thus far, doctors have used a modified virus as a “vector” to target tumor cells. Additional research and clinical trials are needed to determine if this therapy is safe and effective for mesothelioma.
This type of treatment involves the identification and treatment of epigenetic changes that contribute to development of cancer. Treatments are being developed that target the changes and reverse them. Valproic acid is a type of epigenetic treatment that has been investigated in a phase II clinical trial for use in mesothelioma in combination with the chemotherapy drug doxorubicin. In patients who had good performance status and disease that was no longer responsive to traditional chemotherapy, the combination was determined to provide survival benefit. Ongoing studies are needed in this promising treatment area.
This therapy involves the use of a type of drug called a photosensitizer to destroy cancer cells. Following injection of the photosensitizer, specific areas are targeted with light to activate the drug and induce cell death. A 2012 pilot study revealed an overall survival of nearly 32 months for patients who underwent radical pleurectomy and intraoperative photodynamic therapy. For patients who qualify, the therapy is available at select cancer centers throughout the United States.
This procedure involve the administration of nitrogen to “freeze” cancer cells which may otherwise not be visible or amenable to surgical removal. The nitrogen is administered directly onto the affected tissue at the time of surgery. Early stage clinical trials with cryotherapy are currently underway at the Mayo Clinic.
Using viruses to fight cancer is a novel treatment approach. Viruses can be used as vectors for gene therapy, modified to directly eliminate cancer cells, or modified to activate the immune system. The Mayo Clinic is currently conducting a phase I clinical trial investigating the use of the measles virus administered directly into the pleura. Other forms of virotherapy are under investigation as possible mesothelioma cures.