Researchers develop a new approach for treating children with neuroblastoma

A research team from the University of Zurich and the University Children's Hospital Zurich has developed a new approach for treating children with malignant tumors of the nervous system. By combining an approved drug with a specialized diet, they were able to slow down tumor growth and stimulate cancer cells to mature into normal nerve cells.

Neuroblastomas are malignant tumors of the nervous system and rank among the most common and aggressive solid tumors in children. Most affected children are younger than five years of age. Particularly in high-risk neuroblastoma, the prognosis remains poor despite intensive treatment, with only half of children being cured.

Effects of drug boosted

A research team led by Raphael Morscher, research group leader and attending physician at the University of Zurich (UZH) and the University Children's Hospital Zurich, has now developed a novel therapeutic approach together with international partners. The researchers focused on a drug-diet combination with difluoromethylornithine (DFMO), a drug recently approved in Switzerland. DFMO inhibits the production of so-called polyamines, which play a key role in tumor cell growth in children.

We discovered that the effectiveness of DFMO can be more than doubled in mice when a targeted, proline- and arginine-free diet is applied under controlled conditions."

Raphael Morscher, research group leader and attending physician at the University of Zurich (UZH) and the University Children's Hospital Zurich

The diet amplifies the drug's effects by additionally blocking the formation of polyamine precursors.

Reprogramming cancer cells

Rather than destroying the cancer cells, the treatment drives them to mature. This puts a stop to the tumor's unrestrained cell division, and the cells begin to transform into more mature nerve cells - a natural process that is blocked in neuroblastoma.

"The treatment not only slows down tumor growth but also brings about a functional change in the cancer cells," says Morscher, describing the new therapeutic approach. In the pre-clinical mouse models, the tumors grew significantly more slowly or even regressed - and the treatment was well tolerated. It targets protein production in cancer cells by preventing specific genetic blueprints from being correctly read and translated. This changes the cells' function and promotes the maturation of the cancer cells.

Enzyme replaces diet

Raphael Morscher's research team is now collaborating with international partners at the Children's Hospital of Philadelphia and Princeton University to prepare the therapy for clinical application. "To bring this innovative approach into clinical trials, we are using an enzyme that replaces the diet in children. Our goal is to offer affected children a new and gentler treatment option in the future," says Morscher.