A new study delving into the genetic drivers of a rare and aggressive childhood cancer called Malignant Peripheral Nerve Sheath Tumor (MPNST) has revealed metabolic frailties in the cancer cells that might be exploited to improve treatments for patients.

MPNST is a rare and deadly childhood cancer that mainly affects teenagers and young adults. These tumors grow quickly, spread easily, and don't respond well to current treatments. Metastasis is the leading cause of death in MPNST and there currently are no targeted treatments for metastatic disease.

The study, led by University of Iowa researchers Eric Taylor, Ph.D., professor of molecular physiology and biophysics, and Rebecca Dodd, Ph.D., associate professor of internal medicine, identifies a specific metabolic pathway that is critical for MPNST cells' survival and growth, which could potentially be targeted with future therapies.

Targeting cancer metabolism to slow tumor progression

To better understand these tumors, the UI researchers used gene editing to create new research models that closely match the cancer-driving mutations found in patients. Using these models, they then applied state-of-the-art genomic and metabolomic tools to map the metabolic pathways that fuel tumor growth in MPNST.

The study, published in Science Advances, found that these cancers rely on a key metabolic pathway to help them survive oxidative stress and drive tumor growth.

This pathway, known as the Pentose Phosphate Pathway (PPP), metabolizes sugar to produce a critical antioxidant molecule that the cancer cells require to combat oxidative stress. When the researchers blocked the PPP, the tumors grew more slowly and were more vulnerable to chemotherapy.

"This is the first time this specific metabolic pathway has been linked to MPNST tumor growth, making it a completely new target for therapy in this cancer type, " Dodd says. "It opens the door to treatment strategies that haven't been explored before and could lead to more effective treatments and better outcomes for patients who urgently need new options."

The highly collaborative study combined Dodd's expertise in cancer biology with Taylor's expertise in metabolism. The lead author was UI graduate student Gavin McGivney, Ph.D., from Bayard in Guthrie County, Iowa, who was co-mentored by Dodd and Taylor.

McGivney graduated from the UI Cancer Biology graduate program in 2024, and is now a postdoctoral scholar at the University of Chicago. Dodd and Taylor are both members of UI Health Care Holden Comprehensive Cancer Center, and Taylor is a member of the UI Fraternal Order of Eagles Diabetes Research Center.

More information: Gavin R. McGivney et al, Somatic CRISPR tumorigenesis and multiomic analysis reveal a pentose phosphate pathway disruption vulnerability in MPNSTs, Science Advances (2025). DOI: 10.1126/sciadv.adu2906  Journal information: Science Advances