Targeting TR4 nuclear receptor with antagonist bexarotene increases docetaxel sensitivity to better suppress the metastatic castration-resistant prostate cancer progression

  title={Targeting TR4 nuclear receptor with antagonist bexarotene increases docetaxel sensitivity to better suppress the metastatic castration-resistant prostate cancer progression},
  author={Linyi Hu and Yin Sun and Jie Luo and Xiang He and Meihua Ye and Gonghui Li and Yiqun Zhang and Jian Bai and Dahong Zhang and Chawnshang Chang},
  pages={1891 - 1903}
Prostate cancer (PCa) is the second leading cause of cancer death in men in America, and there are no curative options for metastatic castration-resistant prostate cancer (mCRPC). Docetaxel (DTX) has been used as a standard chemotherapy for the mCRPC. However, resistance to DTX is a significant clinical problem as half of patients fail to respond to therapy. The TR4 nuclear receptor has been reported to play an important role in PCa progression, however, its linkage to the DTX resistance… Expand
Cellular rewiring in lethal prostate cancer: the architect of drug resistance
It is hypothesized that the tumour engineers a dynamic response through the process of cellular rewiring, in which it adapts to the therapy used and develops mechanisms of drug resistance via downstream signalling of key regulatory cascades such as the androgen receptor, PI3K–AKT or GATA2-dependent pathways. Expand
Testicular Nuclear Receptor 4 Regulates Proliferation and Apoptosis of Bladder Cancer via Bcl-2
  • Huan Wang, Wenqin Luo, +10 authors Haiyang Wu
  • Medicine
  • Frontiers in Molecular Biosciences
  • 2021
Results indicate that TR4 plays a key role in bladder cancer proliferation, and targeting TR4 would probably be a potential strategy for bladder cancer treatment. Expand
Synthetic Retinoids as Potential Therapeutics in Prostate Cancer—An Update of the Last Decade of Research: A Review
The results of the experimental studies on synthetic retinoids conducted within the last decade are presented to highlight the molecular targets of these compounds and to identify their potential promise in the treatment of PC. Expand
Computational prediction of CRISPR-impaired non-coding regulatory regions
A computational pipeline that uses epigenomic information about regulatory elements for the interpretation of CRISPR mutations in non-coding regions of the genome is introduced and links to established and to novel chemoresistance genes are inferred. Expand


Mechanisms of resistance to systemic therapy in metastatic castration-resistant prostate cancer.
Patients with metastatic castration-resistant prostate cancer (mCPRC) now have an unprecedented number of approved treatment options, including chemotherapies (docetaxel, cabazitaxel), androgenExpand
The role of testicular nuclear receptor 4 in chemo-resistance of docetaxel in castration-resistant prostate cancer
Testicular nuclear receptor 4 (TR4) enhances the chemo-resistance of docetaxel in CRPC and may serve as a biomarker to determine the prognosis of docentaxel-based therapy and as a potential therapy target to combine with docetAXel to better suppress CRPC. Expand
Drug resistance in metastatic castration-resistant prostate cancer
Docetaxel in combination with prednisone is the standard of care in men with symptomatic castration-resistant prostate cancer (CRPC). However, a substantial proportion of men with CRPC do not benefitExpand
Characterisation and manipulation of docetaxel resistant prostate cancer cell lines
This study confirms that multiple mechanisms contribute to Docetaxel resistance and the central transcription factor NF-κB plays an immensely important role in determining docetaxe-resistance which may represent an appropriate therapeutic target. Expand
TR4 nuclear receptor promotes prostate cancer metastasis via upregulation of CCL2/CCR2 signaling
In vitro and in vivo results revealed a positive role of TR4 in PCa metastasis and demonstrated CCL2/CCR2 signaling as an important mediator in exerting TR4 action. Expand
Docetaxel-Resistance in Prostate Cancer: Evaluating Associated Phenotypic Changes and Potential for Resistance Transfer via Exosomes
In vitro observations and preliminary clinical studies indicate that exosomes may play an important role in prostate cancer, in cell-cell communication, and thus may offer potential as vehicles containing predictive biomarkers and new therapeutic targets. Expand
TR4 nuclear receptor increases prostate cancer invasion via decreasing the miR-373-3p expression to alter TGFβR2/p-Smad3 signals
The data suggest that TR4 may increase PCa metastasis via a newly identified signal and targeting these TR4/miR-473-3p/TGFβR2/p-Smad3 signals using TR4 antagonist or TR4-siRNA or miR-373- 3p may allow us to develop a new potential therapeutic approach to better suppress PCa cancer. Expand
Prostate cancer: Antiandrogens reverse docetaxel resistance via ABCB1 inhibition
Bicalutamide had similar effects in vitro and in vivo in androgen receptor (AR)-negative DU145 cells, suggesting that the effect on ABCB1 is independent of the AR, and the development of combination therapies with antiandrogens and docetaxel that could be effective regardless of AR status. Expand
Increased Chemosensitivity via Targeting Testicular Nuclear Receptor 4 (TR4)-Oct4-Interleukin 1 Receptor Antagonist (IL1Ra) Axis in Prostate Cancer CD133+ Stem/Progenitor Cells to Battle Prostate Cancer*
It is found that the expression of testicular nuclear receptor 4 (TR4) is significantly higher in PCa CD133+ stem/progenitor cells compared with CD133− non-stem/proGenitor cells, and this finding provides the possibility of targeting TR4 as a new and better approach to overcome the chemoresistance problem in PCA therapeutics. Expand
Targeting TR4 nuclear receptor suppresses prostate cancer invasion via reduction of infiltrating macrophages with alteration of the TIMP-1/MMP2/MMP9 signals
Mechanism dissection found that knocking-down TR4 in PCa cells suppressed metastasis-related genes including MMP2, with induction of TIMP-1. Expand