Prostate cancer is the second most common form of cancer among men in the world. When detected early, the disease is usually treated by reducing the amount of testosterone. However, many patients become resistant to this treatment, and as a result, the number of available treatments is limited. The hormone triiodo-thyronine or T3 (the active form of the hormone T4), produced in the thyroid gland, can play a key role in the development of prostate cancer. By blocking a receptor for the hormone, the growth of tumor cells in the prostate was inhibited. This is shown in a new study by an international research group led by Umeå University, Sweden, and the Medical University of Vienna.
The receptor in question is called thyroid hormone receptor beta or TR-β. In laboratory experiments, the activation of T3 has led to a sharp increase in the number of prostate cancer cells. This is a suurprise, since most of the regular T3 actions are executed by the alpha isoform of the receptor itself (TR-α). However, when the receptor TR-β was inhibited by a compound called NH-3, it reduced the growth of cancer cells. NH-3 is only used in basic science to block TR-β in experimental settings, an its effect on cancer was then confirmed in animal experiments in mice.d
Tumors treated with NH-3 remained smaller or progressed significantly more slowly. This was shown to be particularly effective in models of prostate cancer that are so-called castration resistant (CRPC). This means that the tumour continues to grow despite treatment that reduces the amount of the male sex hormone testosterone, which usually drives cancer growth. This form is currently difficult to treat clinically. Blocking TRβ with NH-3 worked by leading to the elimination of the androgen receptor signal (AR-α), which is activated by testosterone and then plays a central role in the development of prostate cancer.
NH-3 was a more effective anticancer agent than enzalutamide, and their combined use was synergistic. A review of data from cohorts of patients with prostate cancer supports these findings. In tissue samples, elevated levels of TR-β could be seen in tumours in the prostate compared to those in healthy tissue. In addition, genetic analyses show that mutations in many prostate cancer patients change the signalling pathways for thyroid hormone. In the long term, the discovery may open up a new way of attacking certain types of aggressive prostate cancer.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Scientific references
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