Using a novel zebrafish model, Mayo Clinic researchers have identified a molecule called GAB2 that is highly represented in the malignant cells of many patients with neuroblastoma. Neuroblastoma is a cancer that develops from immature neural cells found in several areas of the body.
The researchers believe that overexpression of GAB2 signals the activation of a protein called SHP2 that drives and maintains neuroblastoma.
"Neuroblastoma is one of the most common solid tumors in infants," says Shizhen (Jane) Zhu, Ph.D., who led the research team. Dr. Zhu says the disease accounts for 10 to 13 percent of all childhood cancer deaths.
"Once neuroblastoma spreads beyond its original site in children older than 18 months, it is considered "high risk" and generally does not respond well to conventional treatments, including high-dose chemotherapy," says Dr. Zhu.
Dr. Zhu says that unlike researchers' experience with other cancer types, efforts to identify molecules that could be developed into drugs to treat high-risk neuroblastoma have not been completely successful. The main reason is that this type of cancer has very few molecular abnormalities that are be suitable targets for drug therapy.
Using zebrafish, Dr. Zhu and her colleagues were able to show that GAB2-SHP2 hyperactivity increases the chances another gene, called MYCN can trigger a cancer.
"Overall, our observations validate the important role of GAB2 plays in regulating the generation of high-risk human neuroblastoma," Dr. Zhu says.
Dr. Zhu's research was reported in the journal Cell Reports in March 2017. This research is part of ongoing research initiatives within Mayo Clinic Cancer Center, and informs the Pediatric Hematology and Oncology practice.
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