A Deadly Cancer Hijacks the Brain to Render Itself Untreatable, Study Finds Leave a comment

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New research this week suggests that an aggressive brain cancer can hijack the brain’s own circuitry to further spread and render itself unstoppable. Researchers in Germany studied glioblastoma cells in mice and in the lab, finding that these tumors use some of the same mechanisms behind normal neuron development and migration to systematically invade the brain. The research may one day allow scientists to develop better treatments for the almost always fatal condition.

Though brain cancer is relatively rare, glioblastoma (also called glioblastoma multiforme or GBM) is the most common kind, accounting for about 15% of primary brain tumors. It’s also one of the most dangerous cancers around. It forms from cells known as astrocytes, which support the neurons, and then quickly spreads throughout the brain. Symptoms tend to be nonspecific at first, including headache and nausea. Treatment is rarely successful, and the cancer frequently recurs, with the average length of survival being less than a year.

One major reason for its invulnerability is that the cancer can seed itself widely throughout the brain, making precise eradication with surgery or other methods much more difficult. GBM tumors also appear to contain a diverse variety of cells, further complicating any treatment. But the exact role and function of these different populations of GBM cells has remained mysterious, according to study author Varun Venkataramani, a brain tumor researcher at Heidelberg University in Germany.

To better understand GBM, Venkataramani and his colleagues combined several different methods of studying these tumors on a molecular and cellular level. One of these techniques, known as a chronic cranial window, even allowed them to view the brain and GBM tumors in mice as they laid awake. They also sequenced the genetics of single cells, letting them see which genes were turned off or on.

Other research has shown that GBM cells form a sort of network with one another, connected by long protrusions known as microtubes, and that these microtubes propagate the cancer further. But the team’s work found that other unconnected GBM cells seem to play a vital role in the cancer’s spread. These cells appear to receive a signal from neurons that goad them to invade other parts of the brain. To accomplish this, the team’s work further suggests, the cancer cells take advantage of the same processes that the healthy brain normally uses to create neurons early on in our development. Neuron signals also seem to fuel the growth of microtubes, and, over time, the unconnected GBM cells join together with the rest of the cancer. Perhaps most creepily, the cancer’s invasion might follow a Levy-like pattern of movement, a term describing the energy-efficient ways that some predators will hunt for food in scarce times.

“Taken together, we indeed see that mechanisms of immature neurons and neural progenitor cells during development are hijacked for invasion,” Venkataramani said in an email to Gizmodo. The team’s work is published in the journal Cell.

These findings will ideally be validated by additional studies from other researchers. And there’s always more that could be learned. The current study, for instance, only looked at GBM cells that were allowed to spread unimpeded, and it’s not clear how they would behave in response to chemotherapy and other treatments.

This kind of basic research is crucial to making the discoveries that could someday lead to new therapies for GBM. Because neurons appear to be an important aspect of how the cancer communicates with itself, it’s possible that one approach to stopping it is to interfere with these signals. The team highlights some possible ways that these signals could be interrupted, though there’s plenty more work that has to be done before we can get to that point.

“We believe that these findings will need to be best tested in clinical trials and we will need to further develop clinical imaging so that we can monitor the invasive nature of these brain tumors more specifically,” said Venkataramani. “Lastly, this study establishes a framework that can be in principle used across all cancer entities, and it will be important to understand how these mechanisms will translate to other tumor types.”