UTSW scientists identify pathway to curb the spread of brain cancer : Newsroom

Amyn Habib MD, Assistant Professor of Neurology

DALLAS – August 09, 2022 – Researchers at UT Southwestern have identified a molecular pathway responsible for the spread of glioblastoma to surrounding brain tissue, as well as an existing drug that inhibits tumor growth in animal models. The findings, published in Cell Biology Natureled to a clinical trial that could offer new hope to patients with glioblastoma, the most common form of adult brain cancer that kills hundreds of thousands of people worldwide each year.

“The invasive property of glioblastoma is perhaps its most formidable obstacle to treatment,” said Amyn Habib, MD, associate professor of neurology, member of the Harold C. Simmons Comprehensive Cancer Center and the Peter O’Donnell Jr. Brain Institute. at UTSW, and a staff physician at the Dallas VA Medical Center. “We have identified a pathway that can suppress this cellular invasion, which could offer a new way to increase survival.”

Despite decades of research, the prognosis for most patients with glioblastoma remains poor, with a median survival after diagnosis of only 15 to 18 months. Part of the challenge in treating this cancer is its invasive nature: glioblastoma tumors invade surrounding healthy brain tissue, sending tentacle-like extensions out of the primary tumor that are impossible to remove with surgery alone and difficult to remove. achieve with chemotherapy.

Researchers at UT Southwest have identified a molecular pathway responsible for the spread of glioblastoma to surrounding brain tissue.

Researchers have long considered the epidermal growth factor receptor (EGFR), a protein found on the surface of cells, to be a driver of this cancer, Dr. Habib explained. In nearly half of glioblastoma patients, the gene that codes for EGFR is amplified, causing glioblastoma cells to produce many more molecular signals stimulated by this protein and causing tumor cells to proliferate. Therefore, Dr. Habib added, several clinical trials have focused on EGFR inhibition – but each has failed to improve glioblastoma prognosis.

EGFR on glioblastoma cells can send these signals in two ways: either unprompted, a state known as constitutive signaling, or when stimulated with proteins called ligands. The differences between these two pathways were considered inconsequential, Dr. Habib said. Thus, patients with glioblastoma with amplified EGFR have been grouped into clinical trials.

In the new study, Dr. Habib and colleagues in the Habib lab and elsewhere showed that when cells with boosted EGFR were stimulated with ligands, this receptor appeared to act as a tumor suppressor, preventing invasion of healthy tissue. both in laboratory and animal models. Further experiments showed that a cytoskeletal protein called BIN3 appears to be responsible for inhibiting this invasion. When researchers gave animals with EGFR-amplified glioblastoma tumors an FDA-approved arthritis drug called tofacitinib that increases the amount of EGFR ligands and BIN3, the tumors remained smaller and were less likely to invade the cells. healthy brain tissue. In addition, these animals survived much longer than animals that did not receive this drug.

Dr. Habib noted that tofacitinib could offer a new way to prolong the life of patients with both an enhanced EGFR and a relatively high level of EGFR ligands, a strategy he and his colleagues will explore during a clinical trial launched in September. For patients without high ligand counts, he added, previously explored strategies to inhibit EGFR could potentially prolong survival.

“These approaches could offer new tools in our arsenal to fight glioblastoma,” Dr. Habib said.

This study was supported by grants from the Department of Veterans Affairs (VA) (2I01BX002559-08) and the National Institutes of Health (1R01CA244212-01A1 and 1R01NS119225-01A1). The VA filed a patent on the use of tofacitinib in glioblastoma, citing Dr. Habib as the inventor.

The clinical trial will be conducted at the Simmons Cancer Center.

To learn more about the trial or other cancer trials at Simmons Cancer Center, contact [email protected]

About UT Southwestern Medical Center

UT Southwestern, one of the nation’s leading academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes and includes 26 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 14 researchers from the Howard Hughes Medical Institute. Full-time faculty of more than 2,900 are responsible for groundbreaking medical advances and committed to rapidly translating scientific research into new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 100,000 inpatients, more than 360,000 emergency room cases, and oversee nearly 4 million outpatient visits annually.

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