Neuroblastoma is a type of childhood cancer that affects the nervous system and is the leading cause of cancer-related death in young children. Some patients have a good prognosis, but those with metastatic tumours often cannot be cured despite modern combinations of surgery, radiation, chemotherapy and immunotherapy.
"The children who survive often have lifelong cognitive difficulties due to the harsh treatment, so there is a great need for new forms of therapies for children with neuroblastoma," says Marie Arsenian Henriksson, professor at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet.
Differentiation therapy is a treatment method used in neuroblastoma that aims to transform cancer cells into more mature and healthy cells. The problem with the current retinoic acid differentiation therapy is that many patients do not respond to treatment, and about half develop resistance.
In collaboration with researchers at Lund University, Marie Arsenian Henriksson's research team has shown that inhibition of two specific enzymes, PRDX6 and GSTP1, could be an alternative to retinoic acid treatment.
Neuroblastoma is characterised by high oxidative stress due to the active metabolism in the cancer cells. Tumours are therefore dependent on antioxidant enzymes such as PRDX6 and GSTP1 to manage the stress and avoid cell death. High levels of these enzymes are associated with a poorer prognosis.
"When we inhibit these enzymes in cell cultures as well as in mouse models, some of the tumour cells die while others mature into active, healthy neurons, impairing tumour growth," says Judit Liaño-Pons, researcher at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet.
In the next step, the treatment will need to be tested in a clinical trial to investigate its safety and efficacy in children. One of the inhibitors has received orphan drug designation from the US Food and Drug Administration for the treatment of a different diagnosis in adults, making it a particularly promising drug candidate, according to the scientists.
The study was funded by the Swedish Research Council, the Swedish Cancer Society, the Swedish Childhood Cancer Fund, the Radiumhemmet Research Funds and Karolinska Institutet. There are no reported conflicts of interest.
Liaño-Pons J, Garde-Lapido E, Fahrig FL, Jäckering M, Yuan Y, Andersson S, Schort L, Esteve M, Mohlin S, Bedoya-Reina OC, Arsenian-Henriksson M.
Combined targeting of PRDX6 and GSTP1 as a potential differentiation strategy for neuroblastoma treatment.
Proc Natl Acad Sci U S A. 2025 Jun 24;122(25):e2427211122. doi: 10.1073/pnas.2427211122