Understanding Glioblastoma Recurrence

A common question many patient families ask about glioblastoma is: why does it recur even after surgery and radiation therapy? Glioblastoma is the most aggressive type of brain tumor, originating from glial cells in the brain, and is classified as Grade 4 by the World Health Organization. With a current 5-year survival rate of approximately 7%, it is one of the cancers with a poor prognosis. Let's explore why, despite decades of research, the survival rate has not significantly improved.

Treatment Resistance in Glioblastoma

Glioblastoma cells are difficult to completely remove through surgery because they deeply infiltrate brain tissue. Furthermore, the blood-brain barrier, which protects the brain, blocks many chemotherapy drugs, making treatment challenging. Even if treatment is temporarily effective, the surviving tumor stem cells can regrow, leading to recurrence. The molecular secrets behind this recurrence and resistance have recently been uncovered through research.

Discovery of OSMR and CLIC1 Proteins

A research team from the University of Ottawa Faculty of Medicine in Canada has identified two proteins, OSMR and CLIC1, that contribute to glioblastoma recurrence. OSMR acts as a conductor of tumor progression, making cancer cells more aggressive and increasing resistance to radiation therapy. However, how this protein achieved these effects remained a mystery until now.

• OSMR: The conductor of tumor progression
• CLIC1: A channel protein embedded in the cell membrane

By analyzing the proteins that work alongside OSMR, the research team discovered that CLIC1 is a key partner in this process. CLIC1 transmits signals that enable cancer cells to survive under stress and spread into surrounding brain tissue, confirming the collaborative action of these two proteins.

A New Turning Point for Treatment Possibilities

The research team conducted experiments using the gene-editing technology CRISPR to remove the CLIC1 gene. The results showed that the binding with OSMR was disrupted, and the signals driving cancer cell proliferation were suppressed, slowing down glioblastoma progression. Notably, even when brain tumor stem cells with CLIC1 removed were implanted into mice, tumor growth was inhibited.

This finding is supported by the research indicating that removing CLIC1 eliminates the ability of glioblastoma cells to spread into brain tissue. This is a significant discovery that could potentially reduce the invasiveness, a primary cause of glioblastoma recurrence.

A Novel Approach Using Monoclonal Antibodies

However, since gene removal is not directly applicable to patients, the research team developed an approach using monoclonal antibodies. Experiments were conducted to block CLIC1 using precisely targeted monoclonal antibodies, and the results were successful. This method holds significant potential for use in conjunction with existing treatments.

According to the Seoul National University Cancer Research Center, approximately 630 people in South Korea are diagnosed with glioblastoma each year. In light of this reality, this research offers new hope for glioblastoma treatment. The research team plans to develop better therapeutic strategies through further validation across diverse patient types.