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The research on chess and cancer has one thing in common: you have to act strategically to defeat your opponent. And that's exactly what the MDC scientists are doing. They seek to make selective only aggressive cancer cells that would otherwise escape chemotherapy – and then lure them into a trap.
In chemotherapy, cytostatic drugs, that is, substances that stop the proliferation of cells, prevent the growth of cancer cells and cause their death. This approach often leads to success but has a number of disadvantages. It has a negative effect on healthy cells and can also cause significant side effects in some patients. In addition, in the case of very aggressive tumors, some cancer cells usually survive the treatment. "The remaining cancer cells are particularly dangerous because they are so modified that doctors often do not know what kind of cancer cells they are dealing with," says Dr. Gaetano Gargiulo, head of Max Delbrück's Molecular Oncology Research Group. Molecular Medicine Center of the Helmholtz Association (MDC). This makes it difficult to choose the right substances for further processing.
Be ready for the next shot of the opponent
In some form of non-small cell lung cancer, chemotherapy often results in cancer cell damage that is almost impossible to treat. Those who develop new treatments should keep this possibility in mind. "As a good chess player, we have to think of several advances instead of just reacting to the current situation," Gargiulo said. With his team and researchers from Dutch professor Maarten van Lohuizen of the Dutch Cancer Institute in Amsterdam, he tested the effectiveness of this technique on mice injected with cells of a particular form of non-small cell lung cancer.
In this form of non-small cell lung cancer, cancer cells produce large amounts of an enzyme called Ezh2. The enzyme suppresses a number of tumor suppressor genes, which normally prevent cells from multiplying in an uncontrolled manner. Agents that inhibit this enzyme and thereby reactivate tumor suppressor genes are currently undergoing clinical trials. "In our mice, this agent initially functioned as expected and inhibited the multiplication of tumor cells, thereby controlling cancer," says Michela Serresi, lead author of the publication and head of the team associated with the research group. Gargiulo.
But the researchers also expected the agent to lose its effect over time. "It is interesting to note that the inflammatory situation has always developed tumor growth," said Serresi. The remaining cancer cells have become even more aggressive as a result of the treatment.
Make the cancer cells aggressive – then move to the box maté
This is precisely where MDC researchers are concentrating their efforts. They intentionally send the tumor cells in this way and prepare them for a trap. "Although cells can be extremely aggressive once they are resistant to the Ezh2 inhibitor, they depend on the inflammatory situation," Gargiulo says. "If we can predict this development, similar to how skilled chess players think about the possible moves their opponents might make, or even deliberately force it to do, we can also fight it selectively." Therefore, in the second stage of therapy, the researchers administered mice with an anti-inflammatory substance – putting the cancer cells in the mate.
However, much remains to be done before patients see the benefits of these new treatment strategies. "If we intentionally make cancer cells more aggressive, we need to know exactly what we are doing," said Gargiulo, adding that it would be necessary, for example, to search for biomarkers that allow clinical scientists to predict clearly in which Strategy patients will actually be effective. "We need to first gather enough data and experience in the lab before we can think about testing this treatment strategy on patients," says Gargiulo.
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