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Glioblastoma spreading strategies discovered


 

Every year, around 7,000 people in Germany develop a brain tumor, and around half of those cases involve a glioblastoma, a particularly aggressive form of the disease. Glioblastomas are incurable, but advances are being made in both diagnostics and therapy. Scientists from the Heidelberg University Hospital (UKHD) and from the German Cancer Research Center (DKFZ) in Heidelberg have discovered a fundamentally new way in which glioblastomas spread within the brain.

This news organization spoke to Wolfgang Wick, MD, medical director of the neurologic clinic at UKHD, about how glioblastomas are treated; the role that vaccinations, recombinant proteins, and parvoviruses play; and what therapeutic approaches might be derived from the discovery of this method by which glioblastomas spread.

Question: Glioblastomas spread through the brain like a fungal network. So how would a glioblastoma currently be treated? The tumor can only be partially removed through surgery.

Answer: Nevertheless, glioblastoma would be operated on. This would have a significant effect. Relieving the strain of the main tumor mass, without generating a new deficit, is prognostically very good for the patient concerned. However, surgery on glioblastoma is never curative.

The reason a cure is not possible is down to the special form and spread of the glioblastoma. Nevertheless, an operation helps. This seems to be because removing the main tumor mass maybe has a positive immunological effect. But it may also be connected to the tumor’s network communication. The surgical intervention stimulates the network by increasing resistance.

If the main tumor mass is decreased through a surgical procedure, this results in an at least temporarily improved starting position for the patient until the mass regenerates. This could also be connected to the fact that tumor communication is not unregulated but is rather in accordance with a certain hierarchy and order, which requires a certain structure and mass.

The other aspect is that support can be requested via this communication. You can imagine that a cell connected to another cell via a conduit receives help from this other cell in the form of organelles by exchanging ions and that, for example, stress or toxicity can be much better balanced out in large networks than in small networks. That means that external attacks, such as a surgical intervention, can be much better balanced by a well-organized network than by isolated cells.

Resistance to chemotherapy

Q: How do irradiation and chemotherapy rank in the treatment of glioblastomas?

A: Irradiation is another therapeutic approach. It causes cells to be stuck in the growth phase of the cell cycle. The cells are not killed through radiation, but they are practically halted. And this arrest of the cell cycle is often sufficient to help people with glioblastomas for a very long time. But the same is true for irradiation as for surgery. This deep network of cells cannot be addressed.

Attempts have been made in the past to reduce the radiation dose to the extent that the brain is no longer damaged by it, but this low dose was then not sufficient to exert any control. If you want to control the tumor, the dose must be high and the volume must be correspondingly low, since there is a clear limit.

Every patient is offered alkylating chemotherapy. At the moment, just one substance is used here in the primary therapy: temozolomide. The problem with this is that two-thirds of tumors in all cells exhibit a resistance to this alkylating chemotherapy, which means that the efficacy of this therapy is highly limited in two-thirds of patients.

In the one-third of patients in whom this resistance is not present, the chemotherapy works fairly well. But even then, it is unfortunately only a matter of time until there is a relapse or disease progression. In my practice, this has always been the case, but there are people who have been living with this disease for 20 years now. There seem to be tumor cells that calmly and silently survive this phase of chemotherapy and then restart the cell cycle at some point.

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