01.03.2024 change 01.03.2024

Dual strategy against 'castration-resistant' prostate cancer

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Scientists intend to block a certain receptor in prostate cancer cells that is responsible for its growth. Known as 5-HT5AR, the receptors near the tumour increase the amount of serotonin, a neurotransmitter called the happiness hormone. However, serotonin also promotes the development of cancer and leads to metastases.

Dr. Przemysław Zaręba from the Krakow University of Technology told PAP about work on new drugs to block the 5-HT5AR receptor and at the same time influence other important processes in cancer cells. The scientist is one of the winners of the Polish National Centre for Research and Development LIDER programme.

Prostate cancer is one of the most common cancers in Europe. Its treatment often limits the action of sex hormones - androgens. But while this may be effective at first, the cancer cells eventually adapt to low hormone levels and develop into difficult-to-fight 'castration-resistant' prostate cancer.

The team led by Dr. Zaręba is working on a new group of substances that may be effective in the treatment of such resistant prostate cancers. The researchers proposed a new approach that involves combining two key proteins - PI3K, which is a new but clinically proven element of anticancer drugs, and the 5-HT5A receptor, an innovative 'switch' for androgen receptors traditionally used in the treatment of prostate cancer.

'The substances we have developed will have the ability to affect both of these proteins simultaneously, which may lead to a synergistic effect, i.e. mutual enhancement of their respective effects. The first research results allow us to hope for the effectiveness of this approach,' Zaręba says.

He explains that prostate cancer cells contain a large amount of the 5-HT5AR serotonin receptor. 'This leads to an increase in the amount of serotonin, known as the happiness hormone, in cancer cells and promotes cancer development and metastasis. Therefore, blocking this receptor may prove to be therapeutically beneficial. Such a blockade reduces the concentration of androgens in the body. An indirect effect on the level of sex hormones may improve patient's response to drugs,’ he says.

Substances that affect the PI3K/AKT/mTOR signalling pathway, which is crucial in the development of prostate cancer and its resistance to traditional treatment methods, have recently been used in the treatment of some cancers. Science has confirmed the interplay between this pathway and signals from the androgen receptor. According to researchers, combined therapy could significantly improve the treatment effects.

Scientists in Dr. Zaręba's team use computer simulations to design new drugs. They try to predict how new molecules will work in the body. Thanks to this, they will find out how to build these substances correctly - as medicines. In addition, they will work on ways to produce compounds in an environmentally friendly way.

'After obtaining the appropriate substances, we will test their effectiveness against cancer. We will examine how new substances affect specific pathways in the body that are responsible for the development of prostate cancer. We will start with tests in test tubes, and then move on to tests on living organisms. We want to confirm that the new drugs are not only effective, but also safe and free of side effects,’ Zaręba says.

The project involves a team of scientists from various fields including chemistry, biochemistry, biology and pharmacology. Most of them have extensive experience in research on anticancer substances. The team plans to commercialise the solution.

PAP - Science in Poland, Karolina Duszczyk

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