Possible new treatment method for metastatic prostate cancer

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The androgen receptor with DIM pocket (pink)

The androgen receptor with DIM pocket (pink)

Researchers at KU Leuven have discovered a promising new method for the treatment of metastatic prostate cancer. In such cases, conventional treatments involve the use of medication to suppress or inhibit the patient’s male hormones in order to slow down the disease. After some time, however, the cancer cells become resistant to that medication. In contrast, the new treatment method inhibits the action of the male hormone even in resistant cells. The study appears today in the American Association for Cancer Research’s authoritative journal Molecular Cancer Therapeutics .

Prostate cancer, the most common cancer in men, is caused by cells multiplying uncontrollably in the tissue of the prostate. The prostate cancer cells can later spread throughout the body and form metastases. At that stage, hormone therapy is often used to slow the growth of the cancer. Treatment of that type blocks the action of the male hormone testosterone.
However, the drugs currently used for this, known as androgen receptor inhibitors, only remain effective for a time, as the tumours become resistant. Discovering new ways to inhibit the action of the male hormone is therefore crucial.

A team led by Professor Arnout Voet and Professor Frank Claessens (KU Leuven) has now discovered an entirely new location on the androgen receptor (the protein that binds testosterone) that drugs can bind to in order to suppress the action of the male hormone and therefore inhibit the growth of the cancer. That location has been named the DIM pocket. Further research also identified molecules and active substances that bind to that DIM pocket.

Because the molecules attach to the DIM pocket, the androgen receptor can no longer bind to the DNA strand and the genes driving the progression of the cancer are switched off.

"We are very pleased that our fundamental research into how the androgen receptor works is being translated into potential new treatments," says Professor Frank Claessens.

"The discovery of this DIM pocket therefore paves the way for completely new treatments and drugs that are going to have an effect on the interaction between proteins such as the androgen receptor. In addition to the molecules we identified, we also have a proof of concept for a treatment of this type. It is important to note that the molecules not only work on their own, but when combined with existing therapies, are even more effective in suppressing the cancer cells. What we now need to do is make the molecules more powerful and ensure there are no side effects when used in humans," added Professor Arnout Voet.

Moreover, the researchers are hopeful that the DIM pocket may also be useful in treating other conditions in which similar receptors play a role.

"We are now going to investigate whether molecules can also bind in the DIM pocket of other receptors, in order to treat other cancers and immune disorders," said researcher Christine Helsen.


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