Researchers have uncovered a novel method to help stop the spread of cancer to the brain.
Researchers at McMaster University have uncovered a novel method to help stop cancer from reaching the brain.
In a recent study published in the journal Cell Reports Medicine, researchers Sheila Singh and Jakob Magolan identified a crucial weakness in metastatic brain cancer that could be targeted with new medications to hinder its progression.
Singh, a professor in McMaster’s Department of Surgery and director of the Centre for Discovery in Cancer Research, points out that brain metastases are becoming more common and are extremely deadly; 90 percent of patients die within a year after diagnosis. She highlights that lung cancer, breast cancer, and melanoma are the most frequent causes of brain metastases.
“We’re improving our ability to cure these primary cancers, but sometimes a small number of cancer cells escape and travel to other areas of the body, including the brain,” she notes. “When that happens, it’s usually a late-stage cancer that resists treatment and is very difficult to manage.”
Magolan, a medicinal chemistry professor in McMaster’s Department of Biochemistry and Biomedical Sciences, describes an organ as an island in an ocean, with cancer functioning like a city emerging on it. He explains that certain cities may build marinas filled with ships that can explore and settle on other islands—these ships represent the rare cancer cells that can metastasize to different organs.
“We have found a way to sink these ships while they’re still on their journey, and likely even before they depart,” he states.
The interdisciplinary research team is focusing on an enzyme called IMPDH, which plays a vital role in the cancer cells responsible for initiating brain metastases. By creating drugs that block this enzyme, they believe they can prevent the formation of brain metastases.
So far, the researchers have produced and tested over 500 candidate molecules—a significant achievement, particularly for an academic setting.
“Normally, a discovery program at a large pharmaceutical company will create around 1,000 molecules before choosing one to move into advanced pre-clinical efficacy and safety trials,” Magolan, who serves on McMaster’s Global Nexus executive committee, explains. “We’re already over halfway through a program similar in scale to that, with promising compounds ready for testing, much of which is being conducted here at McMaster.”
Among the more than 500 molecules analyzed so far, the research team has identified many with strong activity against the targeted enzyme. Currently, they are optimizing these leading compounds before selecting the best candidates for testing in animal studies, laying the groundwork for future human clinical trials.
This extensive study has received $2 million in funding and research support from adMare BioInnovations, primarily driven by staff, students, and trainees in both the Boris Family Medicinal Chemistry Laboratory and Singh Lab.
One of the trainees involved is Agata Kieliszek, a postdoctoral fellow in the Singh Lab and the lead author of the study. Kieliszek expresses her excitement over the potential for this research to establish a new standard of care.
“Brain metastases are the most prevalent brain tumors in adults, and current treatments mainly focus on palliative care,” she says. “With this research, we’ve identified a target that could help slow the growth of brain metastases, which, with further investigation, might provide an alternative treatment for patients currently reliant on palliative options.”
In addition to the groundbreaking potential of their results, the researchers are also hopeful about the wider implications of their study.
“The compounds we’re investigating prevent the spread to the brain, but the mechanisms of metastasis might be similar across various organs,” Magolan notes. “I am optimistic that this research could pave the way for anti-metastasis therapies that could inhibit the spread of other cancer types.”
