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Faced with metastatic prostate cancer, hormone therapy is the reference treatment for controlling the cancer. But sooner or later, cancer cells end up resisting it. An international team has just pierced the mechanism involved and their work offers new treatment prospects.
The mechanism of resistance to hormone therapy designed to treat prostate cancer has just been brought to light. This discovery by an international research team led by the Netherlands Cancer Institute opens new perspectives for treatment.
Finding a counter to resistance to hormone therapy
Prostate cancer is a type of tumor that develops under the influence of hormones, primarily testosterone. Patients with metastatic prostate cancer often receive anti-hormonal therapy, which inhibits the signal sent by testosterone that stimulates tumor growth. Anti-hormonal therapy can keep prostate cancer under control, but after a while the cancer manages to escape treatment. Tumor cells become resistant.
In fact, one of the main challenges today is to fight against resistance to hormone therapy. But the exact process behind this resistance to hormone therapy has until now been a mystery.
Internal clock proteins dampen effects of therapy
An international team of researchers from the Netherlands Cancer Institute studied the prostate tissue of 56 patients with high-risk prostate cancer, who had received three months of anti-hormonal treatment before their surgery. After these three months, their tissues were examined at the DNA level. “We noticed that the genes keeping tumor cells alive despite treatment were suddenly controlled by a protein that normally regulates the circadian clock,” explains researcher Simon Linder, who will receive his doctorate for his research in this study.
Wilbert Zwart, one of the research managers, explains: “These circadian clock proteins acquire an entirely new function in tumor cells in the face of hormone therapy: they keep these cancer cells alive, despite the treatment. This has never seen before”.
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Promising new avenues of research
For Dr. Ivan Pourmir, oncologist at the European Georges-Pompidou Hospital, this result is not surprising. “Many hormones are regulated by the circadian rhythm and things like sleep, for example, can influence their production. It is therefore not surprising that the circadian rhythm influences and that this represents a line of work for researchers”.
This surprising discovery also creates new opportunities. The goal now is to block this circadian protein to further increase sensitivity to anti-hormonal therapy in prostate tumor cells.
Wilbert Zwart thus states: “NOur discovery has shown us that we will have to start thinking outside the box when it comes to finding new drugs to treat prostate cancer and testing drugs that affect circadian clock proteins to increase sensitivity to hormone therapy. Fortunately, there are already several therapies that affect circadian proteins, and these can be combined with anti-hormonal therapies. This track, which allows a form of drug repositioning, could save a decade of research“.