Innovative Enzyme Inhibitor Approach Turns Neuroblastoma Cells into Healthy Neurons in Mice

Researchers from Karolinska Institutet and Lund University in Sweden have developed a promising new treatment strategy for neuroblastoma, an aggressive childhood cancer with limited effective options. This innovative approach involves targeting two antioxidant enzymes, PRDX6 and GSTP1, with specific inhibitors. When these enzymes are suppressed, some neuroblastoma cells in mouse models are induced to mature into healthy nerve cells, effectively reducing tumor growth.

Neuroblastoma primarily affects the nervous system and is a leading cause of cancer-related mortality in young children. While some patients respond well to existing treatments, those with metastatic disease often face poor outcomes despite surgery, radiation, chemotherapy, and immunotherapy. The current standard differentiation therapy, utilizing retinoic acid, benefits only a subset of patients as resistance frequently develops.

The study, titled "Combined targeting of PRDX6 and GSTP1 as a potential differentiation strategy for neuroblastoma treatment," explored the enzyme dependency of neuroblastoma cells. These tumor cells experience high oxidative stress due to their active metabolism and rely heavily on antioxidant enzymes like PRDX6 and GSTP1 to survive. Inhibiting these enzymes not only induces tumor cell death but also promotes maturation into healthy neurons, which hampers tumor progression.

One of the enzyme inhibitors used in this research has received orphan drug designation from the US FDA, indicating its potential for clinical development. The findings suggest that enzyme inhibition could serve as an alternative or adjunct to current differentiation therapies, paving the way for new treatment avenues. Future steps include clinical trials to evaluate safety and effectiveness in children.

This research represents a significant advancement in neuroblastoma treatment research, offering hope for therapies that can induce tumor differentiation while minimizing the harsh side effects of traditional treatments.