Overcoming Resistance in High Risk Medulloblastoma

“‘Reprogramming’ cancer cells to treat high-risk brain cancer.”

What This Project Does

William Weiss
  • William Weiss, MD, PhD
  • Professor of Neurology
    University of California, San Francisco School of Medicine

In the last few years, researchers have learned much more about epigenetics. Epigenetics is the study of how and why certain genes get expressed. This knowledge has allowed scientists to better understand the mutations that cause cancer. The inappropriate expressing and silencing of some genes may cause some types of cancer and make them resistant to treatments that are currently available. A team of international researchers led by William Weiss, MD, PhD at the University of California, San Francisco, has been awarded a $1.88 million grant by CureSearch to investigate their hypothesis that drugs that reprogram the epigenome can improve outcomes for children with high-risk medulloblastoma, a type of brain cancer. Dr. Weiss and his team are working to develop new treatments for high-risk medulloblastoma by identifying mutations in epigenetic regulators, and using drugs that target these mutations.

When cancers are considered high-risk, it is often because they are resistant to treatment. Medulloblastoma is difficult to cure using conventional treatments like chemotherapy. Researchers believe that these cancers are resistant to treatment because they have mutations in a group of genes that control epigenetics, a group of proteins that tell the cell which regions of DNA to read, and which to ignore. To conduct their research, the team will first map the genetic changes (mutations) in genes regulating access to chromatin, which is a complex group of proteins that surround and compact the DNA. Then, based on their findings, they will begin testing medications on high-risk medulloblastoma specimens taken from patients during surgery, and in mice that have been genetically engineered to have this cancer. Their hope is that within three years, they can both identify and develop treatments that can be moved to a Phase I clinical trial in patients.

Potential Impact on Children

Brain tumors are the leading cause of death from cancer in children, and medulloblastoma is the most common type of malignant brain cancer. Patients with high-risk medulloblastoma are particularly resistant to the treatments that currently exist. When children with medulloblastoma are resistant to therapies, they have very few options for treatment and long-term survival tends to be poor. More effective treatments for refractory cancers (those resistant to treatment) are crucial. Dr. Weiss’s work attempts to understand how brain cancer cells are “programmed” by the epigenome, and thus how to “reprogram” them to improve treatments for children with medulloblastoma.

Project Updates

18 Month Research Update

Dr Weiss, at the University of California, San Francisco, studies brain tumors in children. His research focuses on trying to understand how to overcome relapse that is often seen in brain cancer patients following initial treatment. Dr. Weiss is studying the genetic changes in brain tumors following treatment to identify new targets for therapy. The team focuses on medulloblastoma, an aggressive type of brain tumor that shows frequent relapse.

Over the last 18 months, Dr Weiss’ research team has analyzed more than 20 brain tumors from medulloblastoma to find a set of genes that change in patients post-therapy. Their research has uncovered a set of genes involved in epigenetics. Epigenetics is the study of how the environment or other factors, like cancer drugs, affect DNA. The Weiss lab has been actively pursuing three of these gene targets: LSD1, HDAC1 and MYC. Dr. Weiss has been testing FDA approved drugs for these targets in his pre-clinical models of medulloblastoma. By testing pre-approved drugs, Dr. Weiss hopes to get these potential cures to children sooner. This will allow the team to move quickly to determine if these compounds will be effective in treating medulloblastoma. According to Dr. Weiss, funding from CureSearch has enabled his team to focus on “testing drugs that are in the clinic or about to enter trials” that can be used to treat medulloblastoma.


This program supported in part by generous contributions from the Team Jack Foundation. For more information about the Team Jack Foundation, visit www.teamjackfoundation.org.

Overcoming Resistance in High Risk Medulloblastoma was last modified: June 17th, 2015 by Geoff Duncan

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