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Prostate cancer disrupts tumor cell biorhythm to prevent hormone therapy

Prevent resistance

This international research team, which includes researchers from Antoni van Leeuwenhoek, TU / e and Oncode Institute, has now made a surprising discovery in the tissues of patients with prostate cancer who were treated with a testosterone-inhibiting agent. An unexpected class of proteins, namely proteins that normally regulate day and night rhythms, appear to nullify the effects of anti-hormone therapy. “A prostate cancer cell doesn’t have a rhythm day or night anymore,” says Wilbert Zwart, one of the study leaders. “But these ‘day-night rhythm’ proteins have now acquired a completely new function in tumor cells: they keep the tumor cell alive despite therapy of hormones. This has never been seen before.”

Now that researchers have discovered the way to escape this tumor, they want to develop strategies to block it, with the goal of increasing the effectiveness of anti-hormone therapy against prostate cancer.

Zwart continued: “The discovery taught us that for new drugs in the treatment of prostate cancer, we need to think outside the box, testing drugs that affect day-night rhythm proteins, in order to increase sensitivity to hormonal therapy in prostate cancer. . Fortunately, there are already several therapies that influence day and night rhythms. These can be combined with anti-hormone therapy. This lead is a form of drug reproduction made possible, could save ten years of research. “

Research design

The study was done in tissues from 56 high-risk prostate cancer patients. They received anti-hormone therapy for three months before surgery. After these three months, the tissues were examined at the DNA level. “Then we saw that genes that can keep the tumor cell alive despite treatment suddenly came under the control of proteins that normally control the day-night rhythm,” says researcher Simon Linder, who will do his PhD on the study. However, this surprising discovery also opens up new opportunities, because inhibition of these proteins day and night has further shown increased sensitivity to anti-hormone therapy in both tumor cells in the laboratory and in mice.

The results of the study may raise the question of whether a daytime and nighttime rhythm is disturbed due to work schedules, for example, may increase the risk of therapy insensitivity to prostate cancer. “There is absolutely no evidence for this,” says internist-oncologist André Bergman. “Day and night rhythms no longer work in prostate tumor cells. The protein has acquired a completely new function here. This new tumor cell escape route has our full attention now. Follow-up research will show whether preventing this improves cancer treatment. prostate. “

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