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

MPNST is a rare and deadly childhood cancer, which mainly affects teenagers and young adults.

These tumours 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, PhD, professor of molecular physiology and biophysics, and Rebecca Dodd, PhD, 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 tumour progression 

To better understand these tumours, 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 tumour 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 tumour growth.

This pathway, known as the Pentose Phosphate Pathway (PPP), metabolises sugar to produce a critical antioxidant molecule that the cancer cells require to combat oxidative stress.

When the researchers blocked the PPP, the tumours grew more slowly and were more vulnerable to chemotherapy.

“This is the first time this specific metabolic pathway has been linked to MPNST tumour 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, PhD, from Bayard in Guthrie County, Iowa, who was co-mentored by Dodd and Taylor.

McGivney graduated from the UI Cancer Biology graduate programme in 2024, and is now a postdoctoral scholar at University of Chicago.

Dodd and Taylor are both members of UI Health Care Holden Comprehensive Cancer Centre, and Taylor is a member of the UI Fraternal Order of Eagles Diabetes Research Centre.

In addition to Dodd, Taylor, and McGivney, the research team also included UI researchers in the Departments of Internal Medicine, Molecular Physiology and Biophysics, and Radiation Oncology at the UI Roy J. and Lucille A.Carver College of Medicine.

Researchers at Washington University School of Medicine, University of Texas MD Anderson Cancer Centre, and the University of Toronto, were also part of the team.

Source: University of Iowa Health Care