Researchers at Karolinska Institutet and Karolinska University Hospital have discovered that an anti-inflammatory drug candidate, inhibiting the prostaglandin E2-producing enzyme—mPGES-1—in the tumor stroma reduces tumor growth in experimental neuroblastoma models. The findings are published in EBioMedicine and open new treatment strategies for this aggressive childhood cancer.

“High-risk neuroblastoma is the most common and deadly cancer in infants. Novel therapies are highly warranted, in particular if they improve survival without adding adverse side effects,” says Professor Per Kogner at Karolinska Institutet’s Department of Women’s and Children’s Health, who led the study together with Professor Per-Johan Jakobsson at Karolinska Institutet’s Department of Medicine, Solna.

Neuroblastoma is an aggressive nerve cell tumor that is diagnosed early, often before age 2 years, and is stratified into different risk categories: low-risk, intermediate-risk, and high-risk. Children with high-risk neuroblastoma receive intensive multimodal treatment that has increased survival over the years, but survivors have both high risk of life-threatening relapse and severe lifelong side effects. Targeting of the stromal compartment has been suggested as a new strategy to increase survival further and to increase the quality of life of children who survive the disease.

Targeting benign cells

“We found that the dominant cell type in the tumor stroma, benign cancer-associated fibroblasts, were the main producers of prostaglandin E2 in neuroblastoma,” says Anna Kock, PhD at the Department of Women’s and Children’s Health and first author of the study. “These normal cells support the growth of cancer cells and should be targeted since they are more genetically stable than the malignant cells, and, therefore, less prone to develop resistance.”

Assistant Professor Karin Larsson at the Department of Medicine, Solna, who has worked on the project for several years, explains: “Prostaglandin E2 not only mediates fever and pain, but also drives inflammation in the tumors, promoting tumor growth. Inhibition of the enzyme mPGES-1, which catalyzes the production of prostaglandin E2, resulted in reduced tumor growth in experimental neuroblastoma models.”

The researchers believe that the finding could lead to improved survival with fewer side effects for children with neuroblastoma.