Researchers develop treatment that can kill glioblastoma cells in brain pathway

Researchers from McMaster University and collaborating institutions have identified a new pathway that glioblastoma cells exploit to invade the brain, leading to the development of a promising therapy. Published in Nature Medicine on August 2, 2024, the study reveals that existing treatments often fail, with glioblastoma patients typically surviving only a few months post-diagnosis. The new therapy demonstrated the ability to destroy returning cancer cells in over 50% of cases in preclinical animal models.

The research utilized large-scale gene editing to compare glioblastoma gene dependencies at diagnosis and after recurrence. This approach uncovered a signaling pathway involved in axonal guidance that glioblastoma cells hijack to infiltrate brain tissue. The team, led by Sheila Singh and Jason Moffat, aims to block this pathway to prevent tumor spread and eliminate inoperable cells.

The therapy involves targeting the hijacked pathway using various strategies, including a drug from the University of Virginia and a novel CAR T cell therapy developed in collaboration with the National Research Council Canada. This CAR T therapy is designed to recognize and attack tumor cells expressing the protein ROBO1, effectively doubling survival times in animal models of glioblastoma and other invasive brain cancers.

The findings suggest that this innovative CAR T therapy could be a significant advancement in treating glioblastoma and may be applicable to other aggressive brain tumors, warranting further clinical trials.