How can a diet and drug combination starve malignant nervous system tumors? A research team from the University of Zurich and the University Children’s Hospital Zurich may have the answer. 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. Supported in part by the NOMIS Foundation, this groundbreaking research was published in Nature and was featured on its October 16 cover as well as in a Nature News & Views article.
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,” says Morscher. 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.
Go to this University of Zurich release: Targeted Diet Enhances Effects of New Childhood Cancer Therapy
Read the Nature publication: Reprogramming neuroblastoma by diet-enhanced polyamine depletion
Read the Nature News & Views article: A drug–diet combination could improve childhood cancer treatment
Feature image: A specialized diet without the amino acids arginine and proline more than doubles the effectiveness of a approved drug – a new therapeutic approach for children with malignant tumors of the nervous system. (Image: Avesta Rastan, Springer Nature)