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The Cutting Edge

New Therapy Shows Promise to Treat Deadly Brain Tumors

Glioblastoma

Glioblastoma at left-frontal lobe with brain metastasis. Image: Shutterstock

Researchers at the UCLA Jonsson Comprehensive Cancer Center have identified a new way to improve survival rates in treating glioblastoma, one of the deadliest and most difficult-to-treat brain tumors. The approach, tested on a mouse model, combined radiation with an antipsychotic drug and a statin used to lower high cholesterol levels, and it was found to extend the median survival of the mice four-fold compared to radiation alone.

Radiation therapy is part of the standard-of-care treatment regimen for glioblastoma, often helping prolong the survival of patients. However, survival times have not improved significantly over the past two decades. There have been attempts to improve the efficacy of radiotherapy through the use of pharmaceuticals; however, the treatments have been hampered by the normal tissue toxicity of the drugs, as well as their inability to penetrate the blood-brain barrier, which protects the central nervous system.

In this trial, the team in the lab of Frank Pajonk, MD, PhD, professor of radiation oncology and a member of the Jonsson Cancer Center, tested the approach using patient-derived glioblastoma lines provided by the Biospecimen and Pathology Core of the UCLA SPORE in Brain Cancer. They discovered that the antipsychotic drug quetiapine, which acts to block dopamine receptors and is able to rapidly cross the blood-brain barrier, enhanced the efficacy of radiotherapy in glioblastoma.

However, the combination of quetiapine and radiation also provoked a resistance mechanism; it induced the synthesis of cholesterol, which helps glioblastoma cells survive. The researchers used Atorvastatin (Lipitor), which is also able to cross the blood-brain barrier, to target and inhibit the cholesterol-biosynthesis pathway.

The results of the study provide evidence that using quetiapine in combination with Atorvastatin and radiation may help extend the survival for people with glioblastoma. The study authors also point out that this therapy includes FDA-approved drugs that can rapidly be translated into a clinical trial.

— Denise Heady

“Dopamine Receptor Antagonists, Radiation, and Cholesterol Biosynthesis in Mouse Models of Glioblastoma,” Journal of the National Cancer Institute, Febrary 9, 2021


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Spring 2021

Spring 2021
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IN THIS ISSUE
  • The Year that Was
  • A Tale of Two COVIDs
  • New Therapy Shows Promise to Treat Deadly Brain Tumors
  • A Pioneer, a President and a Legacy
  • Team Player
  • Awards and Honors
  • A Special Connection Leads to $29 Million Gift to Advance Genomic Medicine
  • Medical Student Commits to Increasing Opportunities for Minority Students
  • Max Gray Salon Offers Timely Mental Health Tips
  • New Endowed Chair Advances Pediatric Orthopaedics
  • Changing the Paradigm for the Treatment of Sports Concussion
  • Gifts
  • From Russia, with Love
  • The Long Haul
  • How COVID-19 Punished Latinos for Their Hard Work
  • The Natural
  • From a Single Blood Stem Cell, Millions of Diverse T Cells
  • Brain Organoids Grown in Lab Mature on Human Timelines
  • A Method to More Efficiently Isolate and Identify Rare T Cells
  • More Women Embrace “Going Flat” after Mastectomy
  • Brick By Brick
  • Do We Really Want to Return to Normal?
  • Safe Harbor
  • High Percentage of California Youth Struggle with Mental Health Issues
  • Mother and Daughter Send Health Care Workers Virtual Hugs
  • UCLA Donors Join Together to Honor Esteemed Orthopaedic Surgeon
  • Conrad N. Hilton Foundation Establishes Fund to Support Neurological Research at UCLA
  • Memoriam
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