New Therapy Destroys Glioblastoma in Recently Unveiled Pathway

Researchers have discovered a new pathway used by cancer cells to infiltrate the brain and developed a promising therapy that targets this pathway with CAR T cells.

Their study showed significant preclinical success in increasing survival and eradicating tumors in animal models of glioblastoma and other brain cancers.

A team of Canadian and American research groups led by the Singh Lab at McMaster University have discovered a new pathway that is used by cancer cells to infiltrate the brain. The research also reveals a new therapy that shows promise in blocking and killing these tumors.

The research, published today (August 2) in Nature Medicine, offers new hope and potential treatments for glioblastoma, the most aggressive form of brain cancer. With existing treatments like surgery, radiation therapy, and chemotherapy, the tumors often return, and patient survival is limited to only a few months. With this new treatment, the returning cancer cells were destroyed at least 50 percent of the time in two of the three diseases tested in preclinical animal models.

New Findings in Glioblastoma Research

To discover the pathway cancer cells use to infiltrate the brain, researchers used large-scale gene editing technology to compare gene dependencies in glioblastoma when it was initially diagnosed and after it returned following standard treatments. By doing this, researchers discovered a new pathway used for axonal guidance – a signaling axis that helps establish normal brain architecture – that can become overrun by cancer cells.

“In glioblastoma, we believe that the tumor hijacks this signaling pathway and uses it to invade and infiltrate the brain,” says co-senior author Sheila Singh, professor with McMaster’s Department of Surgery and director of the Centre for Discovery in Cancer Research. The research was also co-led by Jason Moffat, head of the Genetics and Genome Biology program at The Hospital for Sick Children (SickKids).

“If we can block this pathway, the hope is that we can block the invasive spread of glioblastoma and kill tumor cells that cannot be removed surgically,” says Singh.

Promising New Therapeutic Approaches

To stop the invasion of cancer cells, researchers targeted the hijacked signaling pathway using different strategies including a drug developed in John Lazo’s group at the University of Virginia, and also by developing a new therapy with help from Kevin Henry and Martin Rossotti at the National Research Council Canada using CAR T cells to target the pathway in the brain. They honed in on a protein called Roundabout Guidance Receptor 1 (ROBO1) that helps guide certain cells, similar to a