On a lab bench in Lund, Sweden, researchers were chasing a molecule used to grow blood stem cells when they stumbled onto a clue about one of the most frightening cancers a child can face. That molecule, called UM171, and a genetic mutation found in aggressive brain tumors both destroy the very same structure inside a cell. It was an unexpected meeting point between two worlds of medicine.
The story begins with UM171, a synthetic molecule invented at Université de Montréal that helps scientists grow more blood stem cells outside the body. Stem cells are the body's blank slates—they can become many different kinds of cells—and doctors want enough of them to transplant into patients with serious blood diseases. In recent years, researchers at Lund University found that UM171 works by using a protein called KBTBD4 to break down an important structure inside the cell, known by the short name CoREST.
Then came the surprise. The same CoREST structure is also broken down by mutations in the KBTBD4 gene—genetic changes found in a subgroup of childhood brain tumors. "Although the causes differ, the result is the same—the structure breaks down," said Agatheeswaran Subramaniam, a researcher at Lund University.
That connection matters because the tumor in question is medulloblastoma, the most common malignant brain tumor in children. It affects around 15 to 20 children in Sweden each year. These tumors are thought to start when immature cells in the developing brain fail to grow up properly and keep dividing instead. They are extremely hard to study in the lab because they form so early in brain development.
The key difference is timing. UM171's effect is temporary. But the mutations cause a long-term shortage of CoREST, leaving cells stuck in a stem cell-like state that may help fuel the tumor. "It is striking that a small molecule and genetic mutations lead to the same effect in the cell," said Rohit Sivaprasad, a doctoral student at Lund.
The most hopeful part came next. The team ran a large drug screen and found that a group of medicines called HDAC inhibitors can reverse the damage caused by KBTBD4 mutations. HDAC inhibitors are drugs that change how genes switch on and off inside cells. Because these drugs are already approved for other uses, the study is an example of drug repurposing—giving an existing medicine a brand-new job. The findings, published in the journal Cancer Gene Therapy, point to a possible road toward future treatments.
The work was done in the lab using blood stem cells, not tumor cells, so there is more to test. "What is fascinating about research is that sometimes you find a fundamental mechanism that can help answer several different clinical questions," Subramaniam said. "The next step is to test whether these drugs work in medulloblastoma tumors." One shared piece of cell machinery, it turns out, could one day help answer questions in two very different fields of medicine.