Protein discovery pulls at the roots of recurring brain cancer
Glioblastoma is an aggressive form of brain cancer, and compounding the threat is the high probability of recurrence following treatment, with dormant tumor cells springing back into action and giving rise to new growths. In a development likened to targeting the roots rather than cutting the weeds, scientists have pinpointed proteins that could help unravel these low-lying but dangerous cancer cells, and demonstrated how this could improve the outlook for sufferers of the disease.
Carried out by researchers at Canada's McGill University, the study takes aim at key players in tumor recurrence called cancer stem cells. These cells can evade the grasp of common treatments like surgery, chemotherapy, radiotherapy, which can be effective at taking out fast-growing cancer cells but often leave these more insidious cells unharmed and free to drive recurrence when the coast is clear.
In this way, cancer stem cells have come to be seen as a type of engine room for persistent cancers, and we've seen some interesting studies that focus on ways they might be taken out of the equation. These have included novel nanoparticles that latch onto and destroy cancer stem cells, designer DNA molecules that hunt them down in the blood, and other molecules that starve them of the nutrients they need to survive.
The McGill University scientists have applied this thinking to brain tumor stem cells in a bid to address the high rates of recurrence among glioblastoma patients. The team started by investigating the way these cells operate, which led them to discover a pair of proteins that regulate the genetic programming behind their behavior. A protein called galectin1 was found to interact with another called HOXA5 to guide this process, and when the scientists intervened, they saw some surprising results.
In preclinical animal models of glioblastoma, the scientists suppressed the galectin1 protein by deleting the gene that codes for it, and found it brought about "significant improvements" in the way the tumors responded to radiation therapy, which in turn boosted the animal's lifespan. Adding to this, the team analyzed databases of glioblastoma patients and found those with low level expression of galectin1 and HOXA5 proteins had the best prognosis.
“What we found was really astonishing for us," says Arezu Jahani-Asl, an Associate Professor of Medicine at McGill University. "After we inhibited the galectin1 protein, the brain tumors simply didn’t grow for several months. To improve patient response to therapy, we must exploit these newly identified vulnerabilities in cancer stem cells.”
The findings further broaden our knowledge around the function of cancer stem cells, and how they might be targeted for better patient outcomes. As their next steps, the researchers intend to use CRISPR to investigate and compare approaches that target the galectin1 and HOXA5 complex in the brain.
The research was published in the journal Cell Reports.
Source: McGill University
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