Brain cancer is the most common cause of cancer-related deaths in children. Researchers hope to better understand how brain tumors arise in order to find more effective treatments.
An expert in pediatric brain cancer joined the faculty at Baylor College of Medicine in 2017 with the help of a First-Time Tenure-Track Award from CPRIT. Stephen Mack was a postdoctoral fellow in cancer epigenetics at the Cleveland Clinic Lerner Research Institute. He joined the Dan L. Duncan Comprehensive Cancer Center.
Mack studies many different types of pediatric brain cancers, but he specializes in a type called ependymoma. The only treatment for these tumors — which hasn’t changed in decades — involves surgery and radiation; the cancer doesn’t respond to chemotherapy. In many cases, the tumors are fatal or recur, sometimes as much as a decade later. The 70 percent of patients who live more than five years often suffer brain damage from irradiation, with significant and long-term neurological consequences as well as poor quality of life.
Pediatric tumors sometimes arise even with no mutations of the patient’s genome. Instead, processes that alter gene expression without affecting the underlying DNA sequence can turn a normal cell into a cancerous one.
Every cell in a human body contains the same genome; what differentiates them is the pattern of gene expression that tells a cell “I am a skin cell,” or “I am a brain cell". In the most aggressive type of ependymoma, typically found in very young children, genes turn on during development to serve a specific purpose and give rise to a particular type of cell. But in ependymoma, these genes stay stuck in the “on” position and cause runaway growth instead.
Genes called “epigenetic regulators” may be the culprit. Mack is screening chemical compounds in his laboratory to try to find one that will help the epigenetic regulator recover its normal function and turn off the stuck gene.
“Clinicians are desperate for something that they can give to these patients,” Mack says,” so if we find a drug that we can test in animal models, that’s all we need to go straight to a clinical trial. There is so much of a need.” He prioritizes compounds that are already known to cross the blood-brain barrier, but says if he finds something else that works, he can find a way to deliver it to the brain.
Mack and his wife, a clinical pediatric oncologist, find the research environment in Houston very rich both scientifically and medically. “We came from a very large system (Toronto) and went somewhere that’s very small (Cleveland),” and we preferred the larger, he said. “In Houston, in addition to having a large medical community to draw on, we find the environment very supportive of young researchers.”
He says the CPRIT award allows him to pursue a number of screening efforts simultaneously. “What I’ve learned through my training is that someone can have a profound impact with large-scale studies if they have a commitment,” he says, “and CPRIT provides the commitment that one might only receive within 5-10 years elsewhere.”
Mack received both his undergraduate and graduate degrees in pathophysiology from the University of Toronto, completing his Ph.D. in the genomics of brain tumors in 2014. That same year, he became a postdoctoral fellow at the Cleveland Clinic.
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