PROVIDENCE – Glioblastoma, one of the most common and aggressive forms of adult brain cancer, has long been considered particularly difficult to treat due to different behaviors by cells within the same tumor.
With these differences, some cells have traditionally responded to treatment while others have not, though scientists haven’t fully understood why. But a new study by Brown University Health researchers has identified a molecule that influences this diverse cell behavior, which could pave the way for new treatment approaches.
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“Traditionally, researchers have focused on the overall behavior of a tumor by studying the average response across all the individual cells, using differences between the cells to interpret the average,” said Dr. Clark Chen, Brown professor and Brain Tumor Program director who led the research team. “Our study fundamentally flipped that approach. Rather than focusing on the average response, we focused on the differences between individual cells within the same tumor, and what we found could change how we treat glioblastoma.”
The researchers found that a small molecule within tumors, miR-181d, controls how much of a repair protein each cell produces. Cells with a higher concentration of this protein are more resistant to chemotherapy and continue to fuel tumor growth as other cells with lower protein levels die.
Administering miR-181d molecules into a tumor can help to level this effect and increase chemotherapy response, the team found.
Gatikrushna Singh, a study collaborator and assistant professor of neurosurgery at the University of Minnesota, called the discovery “an exciting step forward.”
“Scientifically, it helps explain why tumors maintain so much internal variability,” Singh said. “Clinically, it opens the door to gene-therapy strategies that could be truly game changing for many glioblastoma patients.”
The Brown Health team also worked with researchers from VisiCELL Medical Inc., Stanford University and Johns Hopkins University.
Elsewhere, researchers are using the discovery to develop a potential new therapy that could improve patient responses to chemotherapy by leveling miR-181d levels within individual tumors.
Jacquelyn Voghel is a PBN staff writer. You may reach her at Voghel@PBN.com.
