Children’s Medical Center Researchers Tie Gene To Pediatric Cancer, Hope To Spur New Treatments

Dallas researchers have pinpointed a gene that fuels the development of several pediatric cancers, a finding that could serve as an impetus for pharmaceutical companies to develop new cancer treatments that help without using chemotherapy.

A team at the Children’s Medical Center Research Institute at UT Southwesternpublished a white paper in the journal Cancer Cell on Monday tying an overactive gene that typically regulates puberty timing, glucose, and metabolism in children with the development of cancers like neuroblastoma and hepatoblastoma, which accounts for nearly 80 percent of pediatric liver tumors.

The gene, named Lin28b, has been linked to cancer in the past, but those experiments were always done in a culture dish, said Dr. Hao Zhu, a principal investigator at CRI and one of the study’s authors. This study was performed with mice, the first time any researcher has shown the connection inside a living animal. This allows researchers to better investigate how the gene interacts inside the body of an animal.

“We took mice that developed pediatric liver cancer and put them through a clinical trial in which we asked, in those mice, when we get rid of Lin28b, how do they do?” said Zhu, who is also a assistant professor of Pediatrics and Internal Medicine at UT Southwestern Medical Center. “Do they do better, or do they do worse? We found they survived for much longer and had much less cancer for a much longer time when the tumor did not have Lin28.”

An overactive Lin28 gene drives cancer development in children, the study found. And, in essence, it showed removing the gene can help treat the tumor. But there are broader implications: For one, the researchers hope it will motivate drug companies to develop a medicine that targets Lin28.

He said he is already aware of one that is currently developing inhibitors that would work against Lin28.

“It really provides a strong rationale to develop treatment, whereas if you didn’t have this kind of data, people might not be as excited about putting the work into developing the drug,” Zhu said.

The other potential benefit is that there are likely other genes that are associated with cancers the way Lin28 is. The only problem being that they haven’t been researched with the same rigor. Zhu called the findings a “model system” for future research. The team has already launched similar studies of other genes.

“We think there’s a whole world of molecules like this that probably deserve more focused study,” he said.

On average, about 700 American children are diagnosed with neuroblastoma each year. About 500 develop Wilms’ tumor and roughly 100 get hepatoblastoma. In Dallas, more than 100 children were treated for those cancers in the last two years. All of these cancers were tied to an overactive Lin28 gene.