“Exploding Cancer Cells” Explained

Glioblastoma brain morphology

Mouse brain treated with control (left) or Vacquinol-1 (right). Notice the significantly smaller tumor upon treatment with Vacquinol-1.

By now many of you may have seen reports of a new ‘breakthrough’ in cancer research resulting in ‘exploding cancer cells’. These reports are in reference to a new study published in the journal Cell. What exactly does this mean, and how realistic is it to expect this treatment to reach patients anytime soon?

✤ In this study, scientists focused on a very aggressive, essentially incurable type of brain cancer known as glioblastoma. Glioblastomas typically have a lot of things wrong with them, meaning most of our inherent hard-wired cellular defense mechanisms have been overridden. Even worse, glioblastomas tend to harbor a subset of cells known as ‘cancer stem cells’ that are resistant to treatment and can repopulate the tumor following treatment.

✤ The scientists screened a range of compounds for their ability to specifically kill glioblastoma cells in culture (i.e. grown in a petri dish). They identified a compound they named Vacquinol-1 which was highly specific; it had no effect on other types of cells, only glioblastoma cells.

✤ Next, they were curious about the mechanism of cell death and discovered that the cells did not die through apoptosis, i.e. the cell suicide program. However they did find that the cell membranes rapidly changed their shape when treated with Vacquinol-1, indicating that the process had something to do with endocytosis.

✤ Endocytosis is a process by which small molecules are brought into the cell from the outside. The cell membrane forms an invagination (crater-like cups), and the molecules are enclosed in a vesicle (a small bubble) within the cell. When glioblastoma cells were treated with Vacquinol-1, they observed the rapid rounding of cells, the formation of spherical protrusions and irregular bulging of the cell membrane, followed by eventual rupture of the cells through a necrotic-like cell death mechanism. This is the part that has been likened to ‘exploding cells’.

✤ Next, in order to fully understand the cellular signalling mechanisms involved, they looked at which genes are involved in this process of cell rupture. They identified a gene known as MKK4 which is involved in many cellular processes such as growth, inflammation and apoptosis. Although the exact mechanism of this pathway is yet to be identified, when MKK4 is missing, Vacquinol-1 had no effect on the cells, indicating that the MKK4 gene is required for this process.

✤ All this was done in petri-dishes so next they tested Vacquinol-1 on mice that had glioblastomas and found that the compound significantly reduced the size of the tumors. The mice in the control group had a median survival (i.e. half the mice were dead) of 31.5 days. In contrast, only two of the eight Vacquinol-1-treated mice died during the 80 days of the experiment. Clearly, the compound had a very pronounced effect on survival.

✤ Clearly there is a long way to go with this work, which is very promising. But it is important to remember that this has only been done in a petri-dish, zebrafish and mice. It hasn’t been tested in humans. Pre-clinical trials are a while away yet, and while it is tempting to get excited about the idea of ‘exploding cancer cells’, a degree of caution is a must.

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