Molecular Studies of Deadly Brain Tumor Could Lead to Better Treatment
A team of researchers, including scientists and physicians at Barrow Neurological Institute, say their findings could help doctors predict more effective therapies for people suffering from the most common and aggressive type of primary brain tumor.
Led by Anna Joy, PhD, a research assistant professor at Barrow, the team has focused its research on the classification of glioblastomas, grouping these tumors into five subtypes based on a signaling pathway within cells called the RTK/PI3K/AKT/MAPK pathway. When activated, it causes normal cells to grow uncontrollably and become cancerous.
“The RTK/PI3K/AKT/MAPK pathway is the most frequently altered pathway in human cancer, including glioblastoma,” said Joy, who has been researching these tumors for about 15 years. “In addition to promoting tumor growth, it also can determine how a cell responds to therapeutics, including chemotherapy and targeted therapy.”
These researchers are now working to develop a test that would identify a patient’s tumor subtype using tumor tissue that has been surgically removed. The results may then determine the type of chemotherapy the patient receives.
The current standard of care for most people with a glioblastoma is to surgically remove as much of the tumor as possible, followed by radiation and the chemotherapy drug temozolomide.
Temozolomide typically only increases survival by about two and a half months.
“The introduction of temozolomide was the biggest breakthrough in new therapeutics for glioblastoma in the last 20 years ,” Joy said. “This illustrates how difficult it has been to develop new therapeutics for this deadly tumor.”
Evidence suggests one subtype of glioblastoma, called the Secondary-Like subtype, responds extremely well to nitrosoureas, which are a class of anticancer drugs that were the standard of care before temozolomide.
Researchers observed that the median survival for patients with the Secondary-Like subtype, who are estimated to account for about 10 percent of all glioblastoma patients, was increased by about four and a half years with nitrosourea treatment. They are working to validate this observation.
The median survival time for glioblastoma patients is approximately 14 months, and about 9,000 people are diagnosed each year.
Dr. Nader Sanai, director of neurosurgical oncology and the Barrow Brain Tumor Research Center, said researchers have faced several challenges in their search for new glioblastoma treatments.
“For one, the tumor itself is very complicated compared to other tumors,” he said. “Single-agent therapies that sometimes work for other tumors don’t work for these tumors because these tumors find ways around them.”
Another problem is that many drugs do not penetrate the brain well enough to reach a glioblastoma.
Sanai also said noted that research for glioblastoma treatments has not received the amount of resources that has been dedicated to other cancer studies.
“I think this type of research is important because people are looking at better understanding the biology of these tumors, and that’s what Dr. Joy’s research really does,” he said.