The signalling substance IL-6 appears to play a crucial role in the survival of instable cancer cells. The researchers found that an existing anti-inflammatory drug, tocilizumab, which blocks the signalling substance IL-6, inhibits the growth of chromosomally instable cancer cells, both in cultured cells and in mouse models. This means that this anti-inflammatory drug could possibly be used as a medicine in certain types of cancer in the future. Foijer and his team carried out this research in collaboration with UMCG researchers Marco de Bruyn and Marcel van Vugt. Today the results were published in the leading journal Nature.
In order to divide, cells must double their hereditary material, coded on the chromosomes, and divide it equally between two daughter cells. Cancer cells often make mistakes in this process. This is called chromosomal instability (CIN) and leads to cells with an abnormal amount of genetic material. Healthy cells rarely make such mistakes, making chromosomal instability a property that distinguishes cancer cells from healthy cells. This trait drives cancer cell evolution, metastasis and therapy resistance, and is associated with poor prognosis for cancer patients. Chromosomal instability is common in aggressive cancers, such as breast cancer. As a result of this trait, an inflammatory response is activated in cancer cells, but why cancer cells activate this inflammatory response and which molecular mechanism they use, was still unknown.
To find out what happens when the inflammatory response is modulated in cancer cells with chromosomal instability, Foijer and his team investigated the so-called cGAS-STING pathway in laboratory-cultured breast cancer cells. The cGAS-STING pathway is a biological mechanism in cells that enables the immune system to respond to infections and the development of cancer cells. The study by the UMCG researchers showed that the signalling substance IL-6 is essential for the survival of cancer cells with chromosomal instability. Signalling substances are substances that are produced as a result of a reaction in the cell, in this case chromosomal instability, and that switch on a new process, for example cell survival.
In the study, the UMCG team discovered that tocilizumab, an existing anti-inflammatory drug used in rheumatoid arthritis, inhibits the growth of chromosomally instable cancers. They demonstrated this in both mice and laboratory-grown human cancer cells. This anti-inflammatory drug had little effect on most healthy cells, but chromosomally instable cancer cells proved to be very sensitive to it. This offers opportunities for potential cancer therapies, as it allows you to inhibit cancer cells very selectively.
Chromosomal instability is an important trait in cancer cells and causes an inflammatory response that, by using the signalling substance IL-6, helps the cancer cells to survive. These findings therefore offer opportunities in future therapies. By inhibiting IL-6 with tocilizumab, the growth of aggressive cancers may be inhibited. Because tocilizumab is an existing anti-inflammatory drug that is already used in the clinic, Foijer expects that this therapy can be rapidly developed as a cancer drug. He hopes to be able to start clinical trials in the near future to investigate the effect of tocilizumab in patients with cancer. If things go according to plan, Foijer expects the first results in patients in about five years' time.
Read the publication in Nature here
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