Aggressive glioblastoma tumors could be at risk: a groundbreaking discovery has managed to kill cancer cells in mice.
A team of researchers from Gothenburg has developed a method that could trigger stress death of these cells. His studies have shown promising results with glioblastoma, one of the most common and aggressive brain tumors among adults. It is estimated that this disease affects about 19,000 people a year in the EU.
Glioblastoma treatment hasn’t changed much since the early 2000s. and consists of chemotherapy, radiotherapy and surgery. The median survival of a patient diagnosed with this disease is 15 months.
Cancer cells are naturally stressed
“Cancer cells are stressed cells, they end up using stress response mechanisms to their advantage“, says Eric Chevet, head of a cancer research laboratory at the French National Institute of Health and Medical Research (INSERM) since 2015.
“One of the advantages is that they are more resistant, stronger and able to migrate, so better withstand additional stresses such as chemotherapy“, explica a Euronews Next.
In the case of glioblastoma, cells use a protein called IRE1 as part of a stress response mechanism that makes them more resistant to anticancer drugs. This phase is called “target identification.”
the researchers tried to see if influencing this process could weaken cancer cells. And they have just published promising results in the journal iScience. The study was the result of collaboration between researchers from INSERM (France) and the University of Gothenburg (Sweden).
They proceeded in three stages.
First, the Gothenburg team worked on computer models as part of “in silico” research, referring to the silicon in computer chips.
They analyzed some 15 million molecules and ran simulations to predict how they would react with proteins in the body. One of them turned out to be useful: the Z4P molecule.
The second step was a test to examine the impact of that molecule on cancer cells.
They discovered that the Z4P molecule not only made cancer cells less resistant, but also blocked their ability to migrateone of the propensities that make glioblastoma such an aggressive disease.
Finally, the researchers tested their findings in real cells: they used the molecule to attack cancer cells in mice. in combination with a drug called temozolomide (TMZ), a type of chemotherapy traditionally used in glioblastoma.
They found that the combined treatment weakened the resistance of cancer cells to stress and significantly reduced the size of the tumors, and the role of the Z4P molecule was evident.
When TMZ alone was used, the tumors reappeared after a time, between 100 and 150 days. But with the combination of TMZ and the Z4P molecule, all the cancer cells disappeared, and the mice had no cancer relapse after 200 days.
And now that?
Despite these promising results, we are still far from a new drug, let alone a miracle pill.
Chevet warns that It probably won’t be another 15 years before these findings offer a new therapeutic option to patients.and stresses that this is an optimistic prediction, barring bumps in the road.
The molecule must be modified to be more effective against cancer cells and tested in more animals before testing it in humans.
For the next step in this research, the INSERM de Chevet laboratory will collaborate with another French team, the Institute of Chemical Sciences in Rennes.
Down the road, the findings could bring hope for treatments against other types of cancer.
“We have also begun to study the use of our substance in other aggressive tumor forms such as pancreatic cancertriple negative breast cancer and certain liver cancers,” says Leif Eriksson, Professor of Physical Chemistry at the University of Gothenburg and co-author of the study.
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