A combination of researchers from France, Australia and the United Kingdom have uncovered a new drug that can prevent the spread of mesothelioma cancer within the body by activating a particular tumor suppressor gene.
Their findings, presented Nov. 9 at the Symposium on Molecular Targets and Cancer Therapeutics in Dublin, Ireland, came from a Phase I trial involving 29 mesothelioma patients and the drug GSK2256098.
“These findings are important, but preliminary,” summarized Jean-Charles Soria, professor of medicine and medical oncology at South Paris University and head of early drug development at the Institute Gustave Roussy in Paris. “Mesothelioma is a deadly disease without many treatment options, and identification of novel and effective therapies is needed.”
The success of the drug revolves around previous research that showed the gene NF2 , which produces a protein called merlin, becomes inactive in 50 percent of mesothelioma patients, and allows another protein (FAK) to increase activity that spreads the mesothelioma cells.
This new drug has shown an ability to strengthen NF2 and prevent the invasive spread of the cancer cells. Researchers believe that in the 50 percent of mesothelioma patients where the NF2 often becomes inactive, the drug could be especially effective.
“This suggested that if we could inhibit FAK in mesothelioma patients, it might slow or stop the spread of the disease,” Soria said. “Early in the clinical study … a patient with mesothelioma, who had progressed quickly on priory therapies, had prolonged stable disease while on GSK2256098.”
Almost Half of Trial Patients Benefited
From the 29 patients who started taking the drug, 14 had the disease stabilized, nine had progressive disease, three had non-measurable disease and three left the study before evaluation of response. On average, patients taking the drugs had 17 weeks before the mesothelioma progressed. In patients where the NF2 was inactive, the disease progression average was 24 weeks.
Progress in the fight against mesothelioma, which has no cure, has been slow. The standard therapy still revolves around a combination of surgery, chemotherapy and radiation. The majority of patients are not candidates for surgery because the disease already has spread, or their age and declining health precludes them. While chemotherapy drugs have improved, research has shown that cancer patients have an unrealistic view of what it can do. The prognosis for most mesothelioma patients often remains grim, but survivors continue to baffle doctors.
Mesothelioma is caused by exposure to asbestos, which also can cause a range other problems, too. Although asbestos is banned in more than 50 countries around the world, its limited use has continued in the United States and Canada.
Lack of Side Effects Was Promising
The recent study, which provides some much-needed optimism, included nine different centers over France, Australia and the United Kingdom. Patients took the drug in capsule form twice each day at doses that ranged from 300 to 1500 milligrams. The side effects were tolerable.
“The results show that merlin is a potential biomarker in mesothelioma that may enable us to identify a subset of patients who could benefit from GSK2256098 and have longer, progression-free survival,” Soria said.
The study began in July 2010, and it is continuing today as more patients are being enrolled to compile a much larger sample and more critical data. Researchers of cancers like melanoma and meningioma, which also are marked by NF2 and merlin inactivation, could benefit from the findings and are watching it closely.