Overcoming Resistance in High Risk Medulloblastoma: Research Update

Overcoming Resistance in High Risk Medulloblastoma: Research Update

Friday, January 26, 2018

Dr. Weiss, at the University of California, San Francisco, studies high-risk brain tumors in children. High-risk tumors are more aggressive and more likely to relapse. His research is focused on trying to understand how to overcome relapse that is often seen in brain cancer patients following initial treatment. The relapse is caused by the tumor becoming resistant to chemotherapy. Dr. Weiss has identified several therapeutic targets whose activity increases in tumors after chemotherapy. The team focuses on medulloblastoma, an especially aggressive type of brain tumor, that shows frequent relapse and has no known cure. The goal of Dr. Weiss’ research is to test FDA approved drugs or drugs that are currently being tested in adult clinical trials to more rapidly repurpose existing drugs for use in pediatric brain cancer. The hope is to find a therapy that is less toxic that can overcome chemotherapy resistance.

Using genomic analysis, Dr Weiss’ research team has analyzed over 28 brain tumors from medulloblastoma patients to find a set of genes that change in patients post-chemotherapy. Their research points to “epigenetic” changes as the cause for chemotherapy resistance. Epigenetics is the study of how the environment or other factors, like cancer drugs, affects DNA. The Weiss lab has been actively studying three epigenetic targets: LSD1, HDAC1 and MYC. So far, the team has identified commercially developed drugs for each target and has tested these drugs in preclinical studies using advanced animal models of medulloblastoma. By testing pre-approved drugs, Dr Weiss hopes to get these potential cures to children sooner. At the present time, they are focused on a drug targeting HDAC1, and testing its ability to cross the “blood-brain barrier”. Initially, the team had a promising therapy but it was poor in penetrating the brain, therefore it was not a suitable treatment for medulloblastoma. The new compound has a much higher brain penetrance and looks to be very encouraging. Preclinical tests are ongoing to verify the drug is effective for medulloblastoma. Once the preclinical test is complete, the team hopes to move quickly to determine if these compounds will be effective in treating medulloblastoma in pediatric patients.

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