Sheila Singh still remembers the first patient she lost to metastatic brain cancer—a 34-year-old mother whose final months were marked by seizures, confusion, and a treatment plan that could do little more than ease her suffering. That memory drives her relentless pursuit of prevention. Now, Singh and her team at King’s College London and McMaster University have taken a major step forward with a new class of drug candidates that could stop cancers from spreading to the brain before they take hold—by precisely targeting an enzyme called IMPDH2. This approach, detailed in the Proceedings of the National Academy of Sciences, offers new hope for patients facing one of oncology’s most devastating complications.
Brain metastases, which occur when cancers from the lung, breast, or skin travel to the brain, are the most common type of brain tumor in adults. Despite their prevalence, treatment options remain limited and largely palliative, with 90% of patients dying within a year of diagnosis. Current therapies often damage healthy brain tissue or suppress the immune system, leaving patients weakened and vulnerable. Singh’s team is flipping the script: instead of treating established tumors, they aim to intercept cancer cells before they even reach the brain.
The key lies in IMPDH2, an enzyme critical to the survival of cancer cells poised to metastasize. While earlier drugs targeted both forms of IMPDH—IMPDH1 and IMPDH2—they caused widespread side effects because IMPDH1 is essential for healthy immune function. The breakthrough here is selectivity: the new compounds developed by Singh’s team and the McMaster spinout Block Biosciences specifically inhibit IMPDH2, which is overexpressed in metastatic cancer cells but scarce in healthy tissues. This precision could mean stopping cancer without compromising immunity.
Agata Kieliszek, a postdoctoral fellow at McMaster and head of biology at Block Biosciences, explains: “Taking a highly selective approach to eliminating these cancer-initiating cells allows us to strike the right balance between effectiveness and safety.” The team has already synthesized several hundred drug candidates, narrowing in on the most promising compounds for preclinical testing. These efforts are jointly led by medicinal chemists at McMaster and Block, accelerating the path toward clinical trials.
The implications are profound. If successful, this preventive strategy could transform metastatic brain cancer from a death sentence into a preventable condition—especially for high-risk patients, such as those with advanced breast or lung cancer. The work builds on Singh’s earlier research, creating a growing foundation for interception therapy. As drug development progresses, the focus remains clear: stop cancer not when it arrives, but before it leaves.