Researchers at the Children’s Medical Center Research Institute at UT Southwestern (CRI) have identified a gene, Lin28b, which plays a key role in the development of different childhood cancers.
“We and others have found that Lin28b – a gene that is normally turned on in fetal but not adult tissues — is expressed in several childhood cancers, including neuroblastoma, Wilms’ tumor and hepatoblastoma, a type of cancer that accounts for nearly 80% of all liver tumors in children,” Dr. Hao Zhu, a principal investigator at CRI, and Assistant Professor of Pediatrics and Internal Medicine at UT Southwestern Medical Center said in a University’s press release.
Every year in the US, there are 700 children diagnosed with neuroblastoma, 500 with Wilm’s tumor and 100 with hepatoblastoma.
At Children’s Medical Center in Dallas alone, more than 100 children have been treated for those three types of cancers over the last two years.
In a study entitled “Lin28b Is Sufficient to Drive Liver Cancer and Necessary for Its Maintenance in Murine Models” and published in the Cancer Cell journal, the team used genetically modified mice overexpressing the LIN28B gene and discovered that this was sufficient to initiate hepatoblastoma and hepatocellular carcinoma in these mice. Furthermore, they observed Lin28b overexpression in hepatoblastomas, which upon liver-specific deletion resulted in reduced tumor burden, extended latency, and prolonged survival, demonstrating that Lin28b is both sufficient to initiate liver cancer and necessary for its maintenance.
“In our study, we found that overproduction of Lin28b specifically causes hepatoblastoma, while blocking Lin28b impairs the cancer’s growth. This opens up the possibility that pediatric liver cancer patients could one day be treated without resorting to chemotherapy,” Dr. Zhu added in the press release.
Lin28b is a critical factor in stem cell and fetal tissue development, leading the research team to hypothesize that it could also play an important role in the development of certain cancers. Furthermore, because it is usually only expressed in embryos, makes it a possible therapeutic target in cancer, since blocking this gene should have few, if any, side effects in normal tissues.
“We looked at Lin28b in a multitude of ways in mice to study its effects on cancer, from increasing it significantly to deleting it. From this and earlier studies, it appears that Lin28b activates the metabolic pathways that provide the building blocks of growth for certain cancers.” Dr. Zhu explained.
Future research should address if genes related to Lin28b have similar effects on the development of cancer and whether they can be effective targets for potential therapies.
If these findings can be translated into human patients, new strategies to target certain childhood cancers could become a reality.
This study was funded by the National Institutes of Health, the Burroughs Wellcome Fund, the Cancer Prevention and Research Institute of Texas and donors to the Children’s Medical Center Foundation.