Scientists at Virginia Tech have developed a novel drug candidate that may strike at the heart of glioblastoma’s recurrence—its treatment-resistant stem cells.
Key Points at a Glance
- JM2 peptide disrupts cancer-driving protein interactions in glioblastoma stem cells
- Targets cells that survive chemotherapy and radiation, slowing tumor regrowth
- Leaves healthy brain cells unharmed in lab and animal studies
- Developed through collaboration across Fralin Biomedical Research Institute and Carilion Clinic
Glioblastoma is among the deadliest forms of brain cancer, with patients surviving an average of just over a year after diagnosis. Standard treatments—surgery, chemotherapy, and radiation—can temporarily shrink the tumor, but recurrence is almost inevitable. Now, researchers at Virginia Tech’s Fralin Biomedical Research Institute may have discovered a way to change that.
In a study published in Cell Death and Disease, scientists introduced a promising peptide therapy called JM2. Designed in the lab, JM2 targets glioblastoma stem cells—the elusive cancer cell population responsible for regrowing the tumor even after aggressive treatment. These cells can lie dormant for long periods before reigniting cancer progression.
“Glioblastoma stem cells are incredibly adaptable,” said Assistant Professor Samy Lamouille, who led the research. “They resist treatment and reawaken when conditions are right. We needed a way to strike them directly without harming healthy cells.”
The answer came from an unexpected place: connexin 43, a protein that helps form gap junctions between cells. While connexin 43 has been studied for years, Lamouille and his team made a groundbreaking observation—using super-resolution microscopy, they discovered that in glioblastoma stem cells, connexin 43 lines microtubules, structural elements that play key roles in cell division and stability.
Inspired by this discovery, the team developed JM2, a peptide that mimics the part of connexin 43 responsible for binding to microtubules. The goal: disrupt the interaction, and destabilize the cancer cells from within. It worked. JM2 was selectively toxic to glioblastoma stem cells while leaving healthy brain cells untouched. In lab cultures, tumor-like gliospheres visibly shrank. In animal models, tumor growth slowed significantly.
“Seeing those gliospheres collapse in the dish was a powerful moment,” said co-author Rob Gourdie, who originally developed the JM2 peptide. “JM2 had an unexpectedly strong, targeted effect.”
The study was a collaborative effort, combining expertise in super-resolution imaging, cancer biology, and peptide engineering. Clinical samples came from patients treated at Carilion Clinic, underscoring the translational potential of the research.
Though more work is needed before JM2 reaches clinical trials, the early findings are promising. Lamouille’s lab is now exploring delivery systems—such as nanoparticles and viral vectors—to efficiently target JM2 to tumors in the human brain.
Beyond glioblastoma, the research uncovers a new tumor-supporting function of connexin 43, suggesting the approach could be extended to other treatment-resistant cancers. Lamouille and Gourdie have co-founded Acomhal Research Inc. to continue development of JM2 and bring it closer to clinical application.
“It’s rare to find something that hits a cancer’s core like this,” said Lamouille. “With JM2, we’re not just treating a tumor—we’re attacking its source of regrowth.”
Source: Virginia Tech News
