UCLA study finds a novel combination treatment for glioblastoma

A team of scientists from David Geffen UCLA School of Medicine, Dana-Farber Cancer Institute, Roche Innovation Center, and the University of California San Diego have found a new treatment combination that would improve the prognosis of patients with glioblastoma.

The treatment combination, including a FDA-approved anticancer drug called erlotinib and an experimental drug called idasanutlin, worked well in mice. The team hopes to conduct clinical trials to test it in humans.

Findings of the study appear in Nature Medicine.

The corresponding author is Dr. David Nathanson, an Assistant Professor of Molecular and Medical Pharmacology in the David Geffen School of Medicine at UCLA.

Glioblastoma is the most common type of malignant brain tumor among adults. The EGFR gene is frequently mutated in glioblastoma, and mutant EGFR accelerates tumor growth through multiple mechanisms. On the other hand, mutant EGFR makes the tumor more sensitive to a common class of chemotherapy medications, known as EGFR tyrosine kinase inhibitors (TKIs). One example of EGFR TKIs is erlotinib, which is approved by the U.S. FDA for non-small cell lung cancer and pancreatic cancer.

Dr. Nathanson's laboratory focuses on identifying the key processes driving glioblastoma. Its goal is to find new therapeutic strategies to treat this fatal disease. Along with his colleagues, Dr. Nathanson previously discovered that EGFR genetic alterations promote glycolytic gene expression and sugar uptake in glioblastoma cells, conferring significantly shorter survival in patients. They also identified a new mechanism of EGFR TKI resistance. Specifically, glioblastoma cells evade EGFR TKIs by dynamically regulating mutant EGFR.

In the current work, Dr. Nathanson's team tested a combination of erlotinib and idasanutlin in mice implanted with human glioblastoma cells. The brain-penetrant small molecule idasanutlin is known to activate p53 to induce cell death. The researchers found that the combination treatment resulted in tumor regression in mice. Further, they found a way to predict sensitivity to this combination treatment.

Taken together, a combination of erlotinib and idasanutlin represents a potential treatment strategy for glioblastoma.
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