Anti-inflammatories may help with aggressive cancers

The signal substance IL-6 appears to play a crucial role in the survival of unstable cancer cells

UMCG researcher Floris Foijer and his team have discovered that an existing anti-inflammatory agent inhibits the growth of chromosomally unstable cancer cells. They discovered this by unraveling a biological mechanism that is essential for the survival of chromosomally unstable cancer cells. These are cancer cells with many errors in their DNA.

The signal substance IL-6 appears to play a crucial role in the survival of unstable cancer cells. The researchers discovered that an existing anti-inflammatory agent, tocilizumab, which blocks the signal substance IL-6, inhibits the growth of chromosomally unstable cancer cells, both in culture dishes and in mouse models. This means that in the future this anti-inflammatory may be used as a medicine for certain types of cancer. Foijer and his team conducted this research in collaboration with UMCG researchers Marco de Bruyn and Marcel van Vugt. The results were published today in the leading journal Nature.

Survival of unstable cancer cells
In order to divide, cells must duplicate their genetic material, coded on the chromosomes, and divide them fairly between two daughter cells. Cancer cells often make mistakes in this process. This is called chromosomal instability and leads to cells with an abnormal amount of genetic material. Healthy cells rarely make such mistakes, making chromosomal instability a characteristic that distinguishes cancer cells from healthy cells. This property allows cancer cells to evolve, metastasize cancer cells and is associated with a poor prognosis for cancer patients. Chromosomal instability is common in aggressive cancers, such as breast cancer. As a result of this property, an inflammatory response is activated in cancer cells, but why cancer cells activate this inflammatory response and what the molecular mechanism is, was still unknown.

Signal substance IL-6 essential
To find out what happens when the inflammatory response is modulated in cancer cells with chromosomal instability, Foijer and his team examined the so-called cGAS-STING pathway in laboratory-grown breast cancer cells. The cGAS-STING pathway is a biological mechanism in cells that allows the immune system to respond to infections and the development of cancer cells. The study by the UMCG researchers showed that the signal substance IL-6 is essential for the survival of cancer cells with chromosomal instability. Signaling substances are substances that are produced as a result of a reaction in the cell, in this case chromosomal instability, and switch on a new process, for example cell survival.

Anti-inflammatory in rheumatism inhibits IL-6
In the study, the UMCG team discovered that tocilizumab, an existing anti-inflammatory drug given in rheumatism, inhibits the growth of chromosomally unstable cancers. They demonstrated this in both mice and human cancer cells grown in the laboratory. This anti-inflammatory had little effect on most healthy cells, but chromosomally unstable cancer cells turned out to be very sensitive to it. This offers results for possible therapies against cancer, because in this way you can very selectively inhibit cancer cells.

Potential new drug in aggressive cancers
Chromosomal instability is an important property of cancer cells and provides an inflammatory response that, by using the signal substance IL-6, helps the cancer cells survive. These results therefore offer possibilities in future therapies. Inhibiting IL-6 with tocilizumab may inhibit the growth of aggressive cancers. Because tocilizumab is an existing anti-inflammatory drug that is already being used in the clinic, Foijer expects this therapy to be developed quickly as a cancer drug. He hopes to be able to start clinical trials in the short term into the effect of tocilizumab in patients with cancer. If all goes well, Foijer expects the first results in patients in about 5 years.

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