A groundbreaking international study spearheaded by researchers at Umeå University in Sweden and the Medical University of Vienna in Austria has unveiled a previously unrecognized role of thyroid hormone signaling in the progression of prostate cancer. The findings, detailed in the journal Molecular Cancer, highlight the thyroid hormone receptor beta (TRβ) as a critical driver of tumor growth in prostate cancer, opening the door for innovative therapeutic strategies targeting this pathway.
Prostate cancer remains the second most prevalent cancer among men worldwide, with treatment options becoming increasingly limited as the disease advances, especially in forms resistant to conventional hormone therapies. The current mainstay of treatment involves androgen deprivation therapy, which lowers testosterone levels to suppress tumor progression. Unfortunately, many patients develop castration-resistant prostate cancer (CRPC), wherein tumors continue to grow despite reduced androgen signaling. This new study offers hope by identifying an alternative molecular target that could circumvent this resistance.
Central to the research is the thyroid hormone triiodothyronine (T3), which exerts many of its physiological effects by binding to nuclear thyroid hormone receptors such as TRβ. While thyroid hormones are classically known for regulating metabolism, this study uncovers their unexpected influence on the proliferation of prostate cancer cells. In vitro experiments demonstrated that T3 activation induces a marked increase in prostate cancer cell numbers, implicating TRβ as a facilitator of tumor growth.
The research team employed NH-3, a specialized molecular inhibitor of TRβ, to study its effects on prostate cancer models. NH-3 effectively blocks the receptor’s ability to mediate thyroid hormone signals. When applied to cultured cancer cells, NH-3 significantly curtailed their proliferation, indicating that TRβ signaling is not just correlated with but actively contributes to cancer progression. This selective inhibition offers a promising avenue for targeting aggressive prostate tumors.
To extend their findings beyond cell cultures, the researchers conducted in vivo experiments using mouse models implanted with human prostate tumors. Administration of NH-3 led to a pronounced reduction in tumor size and slowed progression compared to untreated controls. These effects were especially prominent in models of castration-resistant disease, which mimic the clinical challenge faced by patients who no longer respond to testosterone-suppressing therapies.
Mechanistically, blocking TRβ disrupted the androgen receptor (AR) signaling cascade, which is ordinarily sustained by testosterone and pivotal for prostate cancer cell survival and growth. By impairing AR signaling through thyroid hormone receptor inhibition, NH-3 indirectly undermines a key growth axis in prostate cancer. This dual blockade strategy could be instrumental in overcoming therapy resistance inherent to advanced prostate cancer.
Supporting the experimental results, the team performed analyses on tissue samples from prostate cancer patients. Elevated levels of TRβ were observed in malignant tissue compared to healthy prostate samples, suggesting upregulation of this receptor is associated with tumorigenesis. Additionally, genetic studies revealed mutations affecting thyroid hormone signaling pathways in a substantial subset of these patients, underscoring the clinical relevance of targeting TRβ.
Despite the promise shown in preclinical models, researchers caution that therapeutically modulating thyroid hormone pathways must be approached with precision. Given the hormone’s systemic roles, unintended disruptions to thyroid function could generate adverse effects. Future investigations will need to define therapeutic windows and explore combinations with existing treatments to maximize efficacy while minimizing risk.
The identification of TRβ as a druggable target heralds a paradigm shift in prostate cancer research, offering a novel molecular foothold against tumors that evade current therapeutic regimens. Continued exploration of thyroid hormone receptor antagonists holds the potential to diversify the arsenal of prostate cancer treatments and improve patient outcomes in what remains a challenging disease landscape.
Beyond prostate cancer, these findings broaden our understanding of hormone-receptor cross-talk in cancer biology, revealing intricate networks that sustain malignancies. The intersection of thyroid hormone and androgen receptor signaling pathways provides new insight into cellular growth regulation and suggests that endocrine factors outside the traditional androgen axis may play pivotal roles in cancer progression.
As the scientific community digests these discoveries, ongoing clinical and translational efforts will be critical to translating them into viable treatments. The journey from bench to bedside, while complex, promises to enrich therapeutic methodologies for what has historically been a difficult-to-manage cancer.
This collaborative research effort exemplifies the power of international and interdisciplinary partnerships in uncovering novel oncological targets. By bridging molecular biology, pharmacology, and clinical oncology, such endeavors accelerate the pace of innovation and offer renewed hope for patients facing resistance to existing therapies.
In summary, the revelation that thyroid hormone receptor beta signaling acts as a critical promoter of prostate cancer growth introduces a new frontier in cancer therapeutics. The targeted inhibition of TRβ could become a key strategy in limiting tumor progression, particularly for cases unresponsive to conventional hormonal treatments, marking a significant step forward in personalized cancer care.
Subject of Research: Human tissue samples
Article Title: Thyroid hormone receptor beta signaling is a targetable driver of prostate cancer growth
News Publication Date: 14-Oct-2025
Web References: 10.1186/s12943-025-02451-2
Image Credits: Medizinische Universität Wien
Keywords: Thyroid hormone receptor beta, TRβ, prostate cancer, triiodothyronine, T3, castration-resistant prostate cancer, androgen receptor, NH-3 inhibitor, hormone signaling, tumor growth, molecular targeted therapy, cancer resistance
Tags: advancements in prostate cancer treatment optionscastration-resistant prostate cancer treatmentshormone therapy resistance in prostate cancerinnovative prostate cancer therapiesMedical University of Vienna cancer studymolecular targets for prostate cancernuclear thyroid hormone receptors in cancerprostate cancer prevalence in menrole of triiodothyronine in cancertherapeutic strategies targeting TRβthyroid hormone signaling in prostate cancerUmeå University prostate cancer research
