Looking Ahead: Combination Offers New Hope For Glioblastoma

A drug combination is showing promise in mouse models and may lead to a new treatment option for patients with glioblastoma.
BY Katie Kosko
PUBLISHED June 20, 2017
Brain tumors are often difficult to treat, especially glioblastoma multiforme (GBM), which is the most aggressive and deadly type of brain tumor.

But now, there may be new hope in extending the lives of patients with GBM. Researchers from The University of Texas Southwestern Medical Center in Dallas have tested a new approach that has proven to destroy GBM in mice. The study was recently published in Nature Neuroscience.

“This could be a groundbreaking treatment. If it works in patients, then it will be an important advance,” Amyn Habib, M.D., associate professor, Peter O’Donnell Jr. Brain Institute and Harold C. Simmons Comprehensive Cancer Center, said in a statement.

Researchers used a combination of Tarceva (erlotinib), which blocks the epidermal growth factor receptor (EGFR) protein, and thalidomide — used as a tumor necrosis factor (TNF) inhibitor. Both are typically used separately to treat lung cancer and arthritis.

The combination was effective in the mouse model; however, neither drug was effective when used alone, said Habib.

The mice were treated once a day for 10 consecutive days. The drugs were given orally. A series of images revealed no tumors in mice after 20 days.

“This could be a new effective treatment for GBM,” Habib said. “EGFR is expressed in the majority of GBM tumors and drugs are available that can inhibit EGFR. However, EGFR inhibition is not effective in this tumor. We found that inhibiting EGFR leads to increased secretion of TNF and activation of a survival pathway in cancer cells. A combined inhibition of EGFR and TNF signaling inhibits tumor growth. Thus, we have identified a way to make EGFR inhibition effective in this tumor.” 

Increased EGFR expression are detected in 40 to 50 percent of GBMs. So, targeting the gene mutation is important in the treatment of GBM, which accounts for 17 percent of malignant brain tumors.

Common signs include headaches, nausea, vomiting and seizures. In some cases, the tumor can cause subtle personality changes and memory loss.

GBMs are more common in men, people who are older than 50 and people of Caucasian or Asian ethnicity. First-line treatment consists of surgery followed by radiation and chemotherapy. Patients with GBM don’t often live long after diagnosis —the median survival is 12 to 14 months — due to its aggressiveness.

Another promising aspect of this study is that the two medications examined have already been approved by the Food and Drug Administration (FDA). Habib said this could speed up the effort at UT Southwestern to organize a clinical trial to test this combination on human patients; however, it will still need FDA approval and funding before a clinical trial can begin.

The authors on the study noted that although these results show great promise, cancers can often adapt to treatments and find new pathways to thrive in. For instance, they said, initially blocking the EGFR protein in patients with lung cancer was successful. But, over time the cells developed resistance to the medication.
“If we can provide a remission or slowing of the disease and extend survival, that’s a big advance in fighting this devastating disease,” said Habib.
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