Nearly half of children diagnosed with neuroblastoma die from the disease. A cancer that develops in the peripheral nervous system, neuroblastoma most commonly appears in children under age 5. But even those who survive face a myriad of lifelong health challenges due to the harsh nature of the treatment.
Pediatric cancer researcher John Powers hopes his research will not only help more children survive the disease, but also improve the quality of life for those who live to grow up.
Powers was recruited in 2018 to Dell Medical School at The University of Texas at Austin, from Boston Children’s Hospital, where he was a senior scientist. With the help of a First-Time Tenure-Track Award from CPRIT, he joins the faculty of the Department of Pediatrics and Dell Pediatric Research Institute, and LiveSTRONG Cancer Institutes.
Most cases of neuroblastoma originate in the adrenal gland, but by the time the cancer is diagnosed, it has already spread to other organs, making treatment challenging. Chemotherapy and radiation are especially hard on young children because they haven’t yet finished growing. These treatments cause lasting tissue damage, and the children who survive may have stunted growth or joint issues, and some may never reach puberty.
“When a six-year-old gets cancer, it’s a tragedy,” Powers says. He hopes to develop treatments that are far less toxic. “It’s not enough to cure the disease,” he says. “The ultimate goal is to cure the disease more safely so the kids can have a normal life afterward.”
Powers is working on a type of treatment called RNA therapy. This would introduce very small pieces of genetic material, called microRNAs, into tumor cells. Some microRNAs, which are naturally occurring, act as signals to turn on or off specific genes. In the case of neuroblastoma, Powers is studying microRNAs that act as tumor suppressors.
He finds neuroblastoma of particular interest because about one quarter of cases of the disease are caused by an abnormal number — hundreds of copies — of a cancer-promoting gene. This gene is normally kept in check by a tumor-suppressor microRNA. But levels of this crucial microRNA are low inside the tumor cells.
The idea would be to administer a tumor-suppressor microRNA as a therapy. One challenge is getting the microRNA to where it can be effective. It’s naturally degraded in the body and doesn’t travel easily into cells where it’s needed. Powers is studying several approaches that would mitigate these factors and enable the microRNA to get where it needs to go.
He’s developing a model for the disease in mice on which he can test microRNA therapy. If he finds a way to get the microRNA inside tumor cells and it shuts them down, this could be a big breakthrough not only for treating neuroblastoma, but potentially for other cancers as well.
One of the reasons microRNA therapy is so promising is that it “is very unlikely to be toxic to other tissues,” he says, “because the levels of these tumor-suppressor microRNAs are already high in other cells; they’re just compromised in the tumor.”
Powers, who grew up in Austin, says, “The CPRIT support really allows me to take a bigger swing at this disease. It enables me to think more translationally, with bench-to-bedside thinking.”
Powers was both an undergraduate and graduate student at UT Austin, receiving his Ph.D. in molecular genetics and microbiology. He was a postdoctoral fellow at Boston Children’s/Harvard Medical School starting in 2006, and became a senior scientist there in 2015.
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