Targeting Androgen, Thyroid Hormone, and Vitamin A and D Receptors to Treat Prostate Cancer

Brigitte Hantusch, Lukas Kenner*, Vesna S. Stanulović, Maarten Hoogenkamp, Geoffrey Brown*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

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Abstract

The nuclear hormone family of receptors regulates gene expression. The androgen receptor (AR), upon ligand binding and homodimerization, shuttles from the cytosol into the nucleus to activate gene expression. Thyroid hormone receptors (TRs), retinoic acid receptors (RARs), and the vitamin D receptor (VDR) are present in the nucleus bound to chromatin as a heterodimer with the retinoid X receptors (RXRs) and repress gene expression. Ligand binding leads to transcription activation. The hormonal ligands for these receptors play crucial roles to ensure the proper conduct of very many tissues and exert effects on prostate cancer (PCa) cells. Androgens support PCa proliferation and androgen deprivation alone or with chemotherapy is the standard therapy for PCa. RARγ activation and 3,5,3′-triiodo-L-thyronine (T3) stimulation of TRβ support the growth of PCa cells. Ligand stimulation of VDR drives growth arrest, differentiation, and apoptosis of PCa cells. Often these receptors are explored as separate avenues to find treatments for PCa and other cancers. However, there is accumulating evidence to support receptor interactions and crosstalk of regulatory events whereby a better understanding might lead to new combinatorial treatments.
Original languageEnglish
Article number9245
JournalInternational Journal of Molecular Sciences
Volume25
Issue number17
DOIs
Publication statusPublished - 26 Aug 2024

Keywords

  • prostate cancer
  • thyroid hormone receptor
  • androgen receptor
  • retinoic acid receptor
  • nuclear hormone receptors
  • vitamin D receptor

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