Category: Research
Mesothelioma Early Detection Test Shows Promise For Improving Treatment Options
Researchers from New York University Langone Medical Center presented promising research this week on a new diagnostic test designed to identify mesothelioma at an early stage.
Mesothelioma is an aggressive cancer of the lining of the lung or abdomen associated with breathing asbestos dust. Because the diagnosis is difficult, the asbestos-related cancer often goes undetected until it has reached an advanced stage, limiting patients’ treatment options.
The NYU cancer researchers used a a new diagnostic blood assay test to identify proteins secreted by malignant mesothelioma tumors. Developed by the biotechnology company SomaLogic Inc., the test measures protein biomarkers found in the blood. Using the simple blood test, the NYU researchers identified 19 biomarkers associated with malignant mesothelioma. The aim is to detect mesothelioma early enough to allow for effective treatments, and improve survival rates and the quality of life for patients with mesothelioma.
In a presentation at the annual meeting of the American Association for Cancer Research, the research team, led by NYU cardiothoracic surgeon Harvey Pass, reported comparing 170 blood samples from 90 patients diagnosed with malignant mesothelioma and 80 patients who had been exposed to asbestos, but who had not diagnosed with cancer. Using the protein detection assay, the researchers detected 15 of 19 cases of stage 1 or stage 2 malignant pleural mesothelioma.
Between 1940 and 1979, approximately 27.5 million people were exposed to asbestos in workplaces in the U.S. Symptoms of mesothelioma typically take 20 to 40 years to appear after asbestos exposure so many people will be diagnosed with mesothelioma in the coming decades who were exposed to asbestos in the 20th century.
Approximately 3,000 new cases of mesothelioma are diagnosed each year in the U.S., and the researchers estimated the disease would not peak for another 20 years.
Targeting Mesothelin To Give Mesothelioma Patients New Therapy Options
An overabundance of the protein mesothelin in a patient’s blood may be a telltale sign of a malignant tumor. Mesothelin is an antibody that is normally produced by cells lining the chest cavity, the abdominal cavity and the lining around the heart. But mesothelin plays a key role in the growth of tumors, studies suggest. The overexpression of mesothelin serves as a marker of various human cancers, including virtually all forms of mesothelioma, a cancer linked to asbestos exposure.
Since mesothelin is found in limited amounts in normal tissue and in overabundance in malignant tissue, researchers have focused on it as a target for cancer immunotherapy.
Researchers have found mesothelin in all mesotheliomas with epithelial cell structures, but not in sarcomatous mesotheliomas. So if they can find ways to get immune system attack cells with mesothelin or knock out the mesothelin, they may be able to starve the mesothelioma tumors.
One of the scientists who has led research on targeting mesothelin is Dr. Raffit Hassan, senior investigator and chief of the solid tumor immunotherapy section in the Laboratory of Molecular Biology at the National Cancer Institute. Dr. Hassan has overseen two successful clinical trials with a third clinical trial about to open on mesothelin.
This month, the Mesothelioma Applied Research Foundation, an advocacy group that funds peer-reviewed research on asbestos-related disease, announced it was presenting its Pioneer Award to Dr. Hassan for his innovative research that offers mesothelioma patients the potential of new treatment options. Dr. Hassan will receive the award at the Meso Foundation’s symposium June 23-25 in Washington, D.C. .
About 2,500 to 3,000 Americans are diagnosed each year with mesothelioma, an incurable cancer. Most have a history of workplace exposure to asbestos, although the symptoms typically take decades to appear.
Peritoneal Mesothelioma Tumors Need Certain Proteins To Grow
Dr. H. Richard Alexander, a highly regarded cancer surgeon and clinical researcher based at the University of Maryland Medical Center, has been systematically studying tumors removed from patients with peritoneal mesothelioma to understand better what causes the tumors’ uncontrolled growth. Dr. Alexander’s aim is to develop new targets for treatment of peritoneal mesothelioma.
Peritoneal mesothelioma is an incurable cancer of the lining of the abdomen caused by ingestion of asbestos particles. But there is great variability in how patients respond to the cancer, with some patients dying rapidly and others living for years. Patients typically don’t notice symptoms of peritoneal mesothelioma until decades after exposure to asbestos, a mineral fiber that was widely used in building materials and is still used in limited applications.
Dr. Alexander and the researchers in his laboratory have been using sophisticated molecular techniques to analyze the proteins produced by thousands of genes and the complex molecular switches and signals that cause mesothelioma cells to grow and divide uncontrollably.
In an article in the January 2011 issue of Cancer, Dr. Alexander and his colleagues report new insights about the roles of certain cellular signaling pathways in malignant peritoneal mesothelioma. The findings may have applications not only for treatment of mesothelioma, but other cancers as well.
The researchers analyzed the gene expression in mesothelioma tumors collected from 41 patients with malignant peritoneal mesothelioma and tracked the patients’ survival. They observed that the patients who died relatively quickly had high levels of certain proteins such as Phosphoinositide 3-kinases and mTOR that are involved with cell growth. The presence of certain proteins in abundance was significantly predictive of patient survival. The researchers hypothesized that the mesothelioma tumors were addicted to the proteins and needed them to grow.
To test the hypothesis, the researchers treated two lines of malignant peritoneal mesothelioma cells with agents to inhibit the proteins and observed a striking reduction in cell signaling and proliferation.
They concluded that characterizing the specific types of genes or proteins that are activated in a patient’s tumor and targeting those may have significant therapeutic value in patients with peritoneal mesothelioma. Such developing medical techniques and search may eventually lead to mesothelioma cancer treatments tailored to the individual patients based on their gene profile, Alexander said.
Australian Mesothelioma Survivor Disease Free Seven Years After Diagnosis
It’s not common, but some people diagnosed with malignant mesothelioma manage to live for years with the disease.
In a recent article in the Journal of Medical Case Reports, Australian researchers report the remarkable case of a 48-year-old Australian woman who remains alive and disease free more than seven years after diagnosis of peritoneal mesothelioma, a cancer of the lining of the abdominal cavity. Both peritoneal mesothelioma and the more common type, pleural mesothelioma, a cancer of the lining of the lung, are signature cancers of asbestos exposure.
The doctors at the University of New South Wales attribute the unnamed woman’s long survival to a combination of factors including early cancer detection, complete removal of the cancerous tumors and treatment of the abdominal cavity with a heated chemotherapy solution—a technique called hyperthermic intraperitoneal chemotherapy. Similar heated chemotherapy treatments are also used on some mesothelioma patients in the U.S.
The current median survival for patients with peritoneal mesothelioma is 10 months. But with the current combined approach of surgical removal of tumors and chemotherapy, about one out of six patients now lives five years, the researchers said.
When the Australian woman was 40, she presented herself to her doctor with abdominal pain, a bad taste in her mouth and tiredness. A CT scan revealed a tumor on the lining of her abdominal cavity, but there were no indications that the disease had spread. When doctors performed surgery, they observed that the mesothelioma affected the small bowel, colon and diaphragm. They removed the cancer tissue from those organs. They then washed the patient’s abdominal cavity for 90 minutes in a warm bath of cisplain and Adriamycin, two powerful chemotherapy drugs.
Two years later, the woman experienced further abdominal pain and underwent another surgical procedure in which small amounts of atypical cells that resembled mesothelioma cells were treated with heated chemotherapy solution. A subsequent CT scan revealed no signs of cancer.
In reviewing the case, the doctors said that three key factors contributed to the woman’s survival. She had a less aggressive form of malignant peritoneal mesothelioma and one that was more responsive to chemotherapy. The cancer had not spread. The patient had the epithelioid type of mesothelioma which is less aggressive than sarcomatous or mixed type of mesothelioma.
In addition, the patient’s tumor tissue had a high expression of estrogen receptor, a genetic switch that appears to suppress te growth of malignant mesothelioma cancer cells, as other recent research suggests. Italian researchers reported that expression of estrogen receptor proteins in mesothelioma patients may help doctors predict how patients will respond to treatment. The manipulation of these proteins may offer a new mode of therapy for treatment of mesothelioma.
NYC Responders Show Pulmonary Disease
New York emergency personnel who responded after the World Trade Center attacks have shown an increased incidence of chronic pulmonary inflammation, researchers at Mt. Sinai reported in a recent clinical study. More than 50,000 men and women were exposed to products of combustion, asbestos and particulate matter after the terrorist attacks on September 11, 2001.
Mount Sinai researchers studied the medical records of almost 20,000 New York firefighters and emergency responders as part of a World Trade Center Monitoring and Treatment Program. The research, published in 2011 in the American Journal of Industrial Medicine, revealed an elevated number of cases of a pulmonary condition called sarcoid like granulomatous pulmonary disease. The average yearly occurrence of the disease among first responders more than tripled from 15 cases per 100,000 in health screenings before Sept. 11, 2001 to 54 cases per 100,000 in 2003 and 2004 —the peak years, according to the new study. Two other studies have reported similar findings.
Sarcoid Like Granulomatous Pulmonary Disease causes inflammation in one or more organs including the lungs and lymph nodes. Granulomas are small tumor-like nodules in the lungs, lymph glands, liver and salivary glands. Granuloma formation may lead to scarring of the lung, known as fibrosis. The cause of the disease is unknown, but it has been linked to multiple environmental and occupational exposures. A portion of those who develop the disease may suffer permanent lung damage.
“Our findings support the hypothesis that environmental exposures generated by the destruction of the World Trade Center may cause ‘Sarcoid like’ Granulomatous Pulmonary Disease,” said Laura Crowley, assistant professor of preventive medicine at Mount Sinai School of Medicine in a press release.
Some research has shown an association between sarcoid like granulomas, sarcoidosis and cancer, but exactly how they are associated remains unclear.
Crowley said monitoring of World Trade Center responders including periodic chest x-rays, must continue so that the NY responders health issues are identified and treated in the early stages.
Philip Landrigan, MD, chair of the Department of Preventive Medicine at the Mount Sinai School of Medicine, said the results of the study clearly support the critical need for ongoing monitoring and treatment for WTC responders.
A medical study published last year in the New England Journal of Medicine reported that New York firefighters and rescue workers who worked at Ground Zero after the 9/11 terrorist attacks still have significantly abnormal lung function years later. Some dust from the World Trade Center destruction contained asbestos and other contaminants, according to the Environmental Protection Agency. Inhaling airborne asbestos is closely associated with respiratory disease including lung cancer and mesothelioma, a cancer of the lining of the lung. Symptoms of mesothelioma typically take 20 to 40 years to appear after exposure to asbestos.
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