Recent research led by a team at the University of São Paulo's Biomedical Sciences Institute has unveiled critical information regarding glioblastoma (GBM), a highly aggressive type of brain cancer. The findings, published in the journal BMC Cancer, focus on the role of the prion protein in the progression of this disease.

Understanding Glioblastoma

Glioblastoma represents one of the most challenging forms of brain cancer, accounting for nearly 49% of all brain tumor diagnoses. In Brazil, it is estimated that between 10,000 and 12,000 new cases arise each year. The survival rate is alarmingly low, with most patients living only around 12 months post-diagnosis. Traditional therapies, including surgery, chemotherapy, and radiotherapy, have not significantly improved patient outcomes over the last two decades.

Despite initial treatment responses, glioblastoma tumors frequently recur in a more invasive form. The current standard treatment employs the chemotherapy drug temozolomide (TMZ), initially approved in the late 1990s. However, a concerning aspect is the persistence of tumor cells, particularly glioblastoma stem cells, which can remain dormant and later reactivate, driving tumor regrowth.

The Role of Prion Protein

The research team, led by Professor Marilene Hohmuth Lopes, investigated the contributions of the prion protein to tumor biology. This protein is crucial for various functions in the central nervous system, aiding in brain functionality and neuronal communication. Lopes noted, “We observed in patient samples that it was elevated in very aggressive tumors, prompting us to explore its relationship with glioblastoma.”

Importance of Tumor Stem Cells

To appreciate the implications of prion protein, one must first understand the mechanism of action within glioblastoma. Traditional treatments primarily target actively proliferating tumor cells, but glioblastoma stem cells are notably resistant to these therapies. Lopes emphasizes, “They can self-renew and generate new cells that recreate tumor hierarchy.” This characteristic underscores the stem cells' role in tumor recurrence after therapies.

Finding a Therapeutic Target

The prion protein's location on the cell surface makes it a viable target for drug intervention. Eduardo Gonçalves, a co-researcher, states, “It’s much easier to target a protein on the surface of the cell than one that is intracellular.” The study demonstrated a significant increase in prion protein levels when glioblastoma stem cells were cultured, indicating its regulatory role.

Utilizing CRISPR-Cas9 technology, the research team edited glioblastoma stem cells' genome to block the production of prion protein. This modification allowed for a decrease in the cells’ invasive and proliferative abilities, suggesting that prion proteins could be pivotal therapeutic targets.

Interplay Between Prion Protein and CD44

Additionally, the study examined the interaction between the prion protein and the CD44 protein—a known cancer stem cell marker. Lopes explained that “we recently discovered that one molecule modulates the other, and we are striving to decode this interaction,” highlighting the complexity of signaling networks in cancer biology.

Protein Role in Glioblastoma Potential for Therapy
Prion Protein Regulates glioblastoma stem cells Targetable on cell surface
CD44 Involved in cancer stem cell invasiveness Potential as a co-target

Future Directions

The research team is clear that while their findings are promising, translating these discoveries into clinical treatments will take time. Lopes remarked, “We work with basic research. It’s a long journey to convert these insights into therapies.” Current focuses include:

  • Understanding how prion protein interacts with other critical genes.
  • Further investigation into signaling pathways that might lead to effective therapies.
  • Exploring combinations of targeting both prion and CD44 proteins for more effective treatment strategies.

Conclusion

As glioblastoma continues to present significant treatment challenges, the identification of novel therapeutic targets like the prion protein offers hope for improving patient survival and quality of life. Continued research in this area is essential to address the complexities of glioblastoma biology.

Literature Cited

[1] Lopes, M. H. et al. (2024). Prion protein regulates invasiveness in glioblastoma stem cells. BMC Cancer.

[2] Medical Xpress. (2025). Prion protein may play key role in progression of glioblastoma. Retrieved from https://medicalxpress.com/news/2025-03-prion-protein-play-key-role.html