When Johanna Hultman, a PhD student at Linköping University in Sweden, set out to study a protein that had long been considered impossible to target with medication, she knew she was taking on a formidable opponent. The protein, called N-MYC, plays a driving role in neuroblastoma, a rare nervous system tumor that almost exclusively affects children under the age of two. For years, researchers had dismissed N-MYC as "undruggable" — too shape-shifting, too slippery for any drug to grab onto. But in a study published in Nature Communications, Hultman and her colleagues have done something remarkable: they've found where two cancer-driving proteins lock together, and they've identified a small molecule that can pry them apart.
"The elusive N-MYC protein was a worthy opponent and presented a real challenge," Hultman said. Yet by combining nuclear magnetic resonance spectroscopy, AI-assisted calculations, and molecular analyses, her team at Linköping University — working alongside Professor Linda Penn's group at the University of Toronto — managed to map the precise anchoring point between N-MYC and a partner protein called Aurora A. Both proteins are implicated in neuroblastoma and many other tumor types. The discovery offers a concrete path forward: a molecule that specifically disrupts their interaction, rather than trying to silence MYC proteins directly, which has stymied drug developers for decades.
The reason MYC proteins have confounded science is structural. Most proteins have a stable three-dimensional shape that drug molecules can latch onto — think of Legos clicking together. N-MYC, by contrast, is in constant motion, reshaping itself like a living blob. "Classic medical drug development is based on the fact that there is a pocket on the protein that you block," explained Professor Maria Sunnerhagen, who leads the structural biology research group. "But MYC keeps changing shape." That's why the field has long called it undruggable.
Neuroblastoma accounts for roughly 6 percent of all childhood cancers, and about half of diagnosed children have high-risk tumors with lower odds of cure. For these families, the new findings represent more than an academic milestone. The research team is careful to note that药物 development takes years, but they're handing off their discoveries to the next stage of clinical research. "We're very pleased that in this particular case, which is relevant to childhood cancer, we have gained some more understanding about how these proteins find and bind to each other," Sunnerhagen said. "We can now hand over the baton to other researchers."
It's a moment of hard-won optimism in a field where progress is measured in decades and centimeters. For the children and families facing neuroblastoma, this study doesn't promise a cure tomorrow — but it draws a clearer map to one.