CureSearch for Children's Cancer funds and supportstargeted and innovative children's cancer research with measurableresults, and is the authoritative source of information and resourcesfor all those affected by children's cancer.
"'Reprogramming' cancer cells to treathigh-risk brain cancer."
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.
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.
Brain tumors have long been one of the most difficult cancers to treat in children. One of these brain tumors, medulloblastoma, is also quite rare and it has not been studied in as much detail as other cancers like leukemia and lymphoma. In order to test new treatments on a type of cancer, researchers have to do a lot of preclinical work that shows why the treatment could be effective. This preclinical work might involve understand the genetics of the cancer, developing cell cultures of the cancer cells, or creating other models of the tumors. In order to do this, researchers need a lot of genetic information.
Dr. Weiss's team studies the genes involved in medulloblastoma and other brain tumors. They have recently discovered parallels between the genes involved in medulloblastoma and the genes involved in other, more common, cancers. These parallels have allowed them to apply insights used to develop therapies for other cancers to developing therapies for brain tumors. For instance, a protein called LSD1 has been shown to be a regulator that affects the development of several types of tumors. Dr. Weiss's team has recently discovered that LSD1 plays a big role in a certain sub-type of medulloblastoma. Because there are already FDA approved compounds that target LSD1, the team can move quickly to determine if these compounds will be effective in treating medulloblastoma, as well. 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.
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