(Vienna, 19-12-2023) Many patients with prostate cancer develop androgen-independent tumor growth, which is referred to as castration-resistant prostate cancer (CRPC). In these patients, activation of the androgen receptor (AR) in the tumors no longer requires androgen stimulation, and therapy with androgen inhibitors becomes ineffective. It is therefore important to identify new additional treatment options for these patients. Against this background, the project "Thyroid Hormone Receptor β/AR Interplay in Prostate Cancer", led by Brigitte Hantusch from MedUni Vienna's Department of Pathology, is being funded with around 390,000 euros.
Elevated levels of the thyroid hormone triiodothyronine (T3) have long been associated with a poorer prognosis of cancer. Based on studies in which the T3-binding protein CRYM was identified as a decisive factor for the availability of T3 in prostate cancer cells, the focus has now shifted to the signaling pathway driven by T3. The focus here is on the thyroid hormone receptor β (TRβ) as a key signaling molecule. The research group led by Prof. Lukas Kenner and Assoc. Prof. Brigitte Hantusch found that TRβ is increasingly expressed in more aggressive forms of prostate cancer and is associated with a poorer prognosis. In vitro experiments have shown that T3 drives the proliferation of prostate cancer cells and accomplishes this by enhancing androgen receptor (AR)-driven gene expression.
In the individual project now funded by the FWF, the researchers want to investigate in detail whether TRβ regulates the genes essential for the growth of prostate cancer autonomously or in cooperation with the AR. Various experimental approaches will be used to clarify the extent to which the two hormone-driven signaling pathways overlap, whether there is reciprocal regulation and whether the two receptors may even interact directly with each other. Specific inhibitors of the receptors are also used for this purpose.The molecular results will be correlated with analyses of histopathological tumor samples and clinical parameters of the patients in order to identify predictive patterns.
This project will contribute to the understanding of hormone-dependent growth of prostate cancer to improve prognostic approaches and potentially lead to the development of innovative therapeutic strategies. The funding amount is € 385,434 over a period of three years.
Further information:
https://www.fwf.ac.at/en/research-radar/10.55776/P37116