At MUSC Hollings Cancer Center in Charleston, Dr. Jezabel Rodriguez Blanco's team is hunting for a solution to one of pediatric oncology's cruelest paradoxes: a cancer that often responds to treatment, only to return devastated. About 30% of children with medulloblastoma—the most common malignant brain tumor in kids—will experience relapse, and when they do, long-term survival drops to nearly zero.
The problem isn't the initial tumor response. The challenge lies in a small but formidable population of cells within the tumor itself. These cells divide slowly, resist standard treatments, and possess the biological machinery to spark a cancer's return. While chemotherapy and radiation attack rapidly dividing tumor cells, these slow-growing outliers slip through the cracks, waiting to fuel regrowth. Understanding this dynamic became the foundation for Blanco's research, published recently in Cell Death & Disease.
The breakthrough centers on a protein called CK1α, which regulates two critical cancer pathways: GLI, which drives tumor growth, and WNT, which enables tumor self-renewal. Blanco's team tested pyrvinium, an FDA-approved drug gaining attention in cancer research for its ability to block GLI signaling. By activating CK1α, pyrvinium simultaneously suppressed both pathways—a dual attack that distinguishes it from treatments targeting only one biological route.
In preclinical models, the results were striking. Pyrvinium blocked medulloblastoma self-renewal, extended the time to relapse, and reduced overall relapse risk. This dual-pathway approach proved more effective than single-target strategies, which often shrink tumors initially but miss the cells driving regrowth. "Cancer cells are very good at escaping when you hit just one pathway," Blanco explained. "If you hit both, you have a better chance of preventing that escape."
The research builds on Blanco's earlier work showing that GLI inhibition alone could slow tumor growth. But the new study reveals something more promising: that hitting both pathways through a single repurposed drug might offer what single-target treatments have not—lasting protection against relapse.
Yet Blanco is careful not to overstate the moment. The work remains in early preclinical stages, and one major obstacle looms: pyrvinium does not easily cross the blood-brain barrier, the biological fortress that protects the brain. A drug that works brilliantly in test models must first reach the tumor to help patients. The team addressed this by testing a modified version of the drug designed to penetrate the brain, with promising results in their models. The next phase involves developing and refining this compound to ensure it is both effective and safe for use in children—a lengthy, rigorous process ahead.
For young medulloblastoma patients, the stakes of this research extend far beyond survival statistics. Current therapies, while life-saving, can leave lasting developmental and health consequences. A treatment that reduces relapse risk could spare children and families from the trauma of recurrence and allow them to move forward with fewer scars. Blanco's work represents a narrow but crucial window of hope—not yet a cure, but a careful, science-driven path toward one.