TGen-led study suggest a drug combination that might prove effective for 1 in 3 glioblastoma patients

TGen-led study suggest a drug combination that might prove effective for 1 in 3 glioblastoma patients

Based on the findings of a new study led by the Translational Genomics Research Institute (TGen), part of City of Hope, a coast-to-coast clinical trial is planned that, if successful, could lead to FDA approval of the first new drug treatment in more than a decade for glioblastoma, the most common and aggressive type of brain cancer.

Using precision medicine to select only participants with a specific genomic “signature of vulnerability,” researchers expect the new treatment could help up to a third of all glioblastoma patients. An estimated 18,000 Americans are expected to die this year from brain cancer, the nation’s seventh leading cause of cancer death.

Results of a preclinical study published in Neuro-Oncology suggest that a drug combination of MLN4924, also known as Pevonedistat, when given in combination with a second drug called Etoposide, could help glioblastoma patients whose cancer cells have lost PTEN, a tumor-suppressor gene.

Genomic sequencing of patient-derived tissue samples showed those samples with a loss of PTEN also showed a spike in the expression of a gene called TOP2A, which research suggests resists the effectiveness of MLN4924. By using Etoposide to block TOP2A, researchers believe glioma cells will be weakened enough for MLN4924 to kill the cancer.

“I’m greatly encouraged,” said Michael Berens, Ph.D., head of TGen’s Glioma Research Lab, and one of the study’s senior authors. “There hasn’t been a new drug approved for glioblastoma in 13 years. Knowing the right patients to enroll in the clinical trial, through study of molecular features of sensitive and resistant tumors, and only treating patients whose tumors have the signature of vulnerability, should set us on a path to a new approved drug treatment.”

The last drug to receive FDA approval for glioblastoma was Avastin in 2009. The average patient survival for glioblastoma remains stuck at about 15-18 months.

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The Phoenix Bioscience Core is home to more than 20 companies, including the Translational Genomics Research Institute, or TGen. The PBC often highlights research happening around the universities, companies and other organizations, which you can read here.

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