Glioblastoma is notoriously difficult to treat and manage. The cancer is not only aggressive and quickly spreading, but is often treatment-averse. Because of this, glioblastoma comes with a poor prognosis of around 15 months of survival following diagnosis. Researchers are urgently working to develop new therapeutic options for patients with glioblastoma – and new research avenues to better understand this cancer. According to News Medical, some researchers and scientists are looking to viruses to expand their understanding. 

The Research

Cancer cells produce more quickly than normal, healthy cells. Breaking a double-strand of DNA can stop this replication and kill the cancer cells overall. In this particular study, a research team found that glioblastoma tumors highly express dNTP (a type of DNA building block) and SAMHD1, a protein. SAMHD1 is interesting; it can both destroy dNTP (causing those double-strand breaks) and repair and rebuild these breaks. 

In the study findings, published in Cancers, the scientists explained that high dNTP levels were expected. After all, high levels of dNTP contribute to cancer proliferation. However, the researchers were also surprised to discover the high level of SAMHD1, as they felt high levels of SAMHD1 would be protective against glioblastoma. Therefore, the research team believes that glioblastoma tumors are able to change the way SAMHD1 functions, driving (rather than protecting against) the tumor.

Employing Viral Insights for Glioblastoma

Because SAMHD1 and dNTP were so highly expressed in glioblastoma, researchers wondered what would happen if they reduced SAMHD1 levels. They chose to do so through using viral protein X (Vpx). The researchers used a viral vector to deliver Vpx to the tumor. This made the tumors more vulnerable to treatment, reduced cancer cell growth and proliferation, and contributed to double-strand breaks that could further halt glioblastoma progression. 

Further, the findings were verified in mice models of glioblastoma. Lower SAMHD1 correlated with less tumor growth. When researchers genetically removed SAMHD1 from these mice models, survival also improved. The research team ultimately hypothesizes that high SAMHD1 levels act protective for the glioblastoma tumor itself. 

Moving forward, researchers will look to SAMHD1 as a potential therapeutic target for glioblastoma. By learning more about this protein, dNTP, and their roles in cancer proliferation, researchers hope that – at some point in the future – there could be a more effective way to treat this cancer. 

What is Glioblastoma?

Glioblastoma, a rare type IV astrocytoma, is an aggressive brain tumor that begins in star-shaped astrocyte cells. It typically begins in the cerebrum but, as these tumors can make their own blood supply, may grow to other areas of the brain. An estimated 20% of brain tumors are glioblastoma. Around 12,000 cases of glioblastoma are diagnosed in the United States each year. Men are more likely to develop glioblastoma tumors than women. In many cases, the cause of this cancer is unknown. Risk factors include radiation therapy and pre-existing genetic disorders. Symptoms can (but do not always) include: 

• Changes in mood, behavior, and personality
• Double or blurred vision
• Nausea and vomiting
• Changes in ability to feel temperature 
• Loss of balance and coordination
• Mental confusion
• Changes in ability to understand or engage with language
• Difficulty thinking or speaking
• Persistent headaches
• Seizures