ASC-J9® increases the bladder cancer chemotherapy efficacy via altering the androgen receptor (AR) and NF-κB survival signals

There have been critical problems in the non-surgical treatment for bladder cancer, especially residence to intravesical pharmacotherapy, including BCG immunotherapy, cisplatin-based chemotherapy, and radiotherapy. Recent preclinical and clinical evidence has suggested a vital role of sex steroid hormone-mediated signaling in the progression of urothelial cancer. Moreover, activation of the androgen receptor and estrogen receptor pathways has been implicated in modulating sensitivity to conventional non-surgical therapy for bladder cancer. This may indicate the possibility of anti-androgenic and anti-estrogenic drugs, apart from their direct anti-tumor activity, to function as sensitizers of such conventional treatment. This article summarizes available data suggesting the involvement of sex hormone receptors, such as androgen receptor, estrogen receptor-α, and estrogen receptor-β, in the progression of urothelial cancer, focusing on their modulation for the efficacy of conventional therapy, and discusses their potential of overcoming therapeutic resistance.

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Androgen Receptor (AR) Transcriptionally Inhibits Programmed Death Ligand-1(PD-L1) Expression to Impact Bladder Cancer Cell Immune Escape

SSRN Electronic Journal ◽

10.2139/ssrn.3946279 ◽

2021 ◽

Author(s):

Anran Sun ◽

Yu Luo ◽

Wen Xiao ◽

Zhipeng Zhu ◽

Hongyu Yan ◽

...

Keyword(s):

Bladder Cancer ◽

Androgen Receptor ◽

Cancer Cell ◽

Immune Escape ◽

Bladder Cancer Cell ◽

Programmed Death Ligand 1 ◽

Programmed Death

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The Long Non-Coding RNA XIST Interacted with MiR-124 to Modulate Bladder Cancer Growth, Invasion and Migration by Targeting Androgen Receptor (AR)

Cellular Physiology and Biochemistry ◽

10.1159/000480419 ◽

2017 ◽

Vol 43 (1) ◽

pp. 405-418 ◽

Cited By ~ 46

Author(s):

Yaoyao Xiong ◽

Long Wang ◽

Yuan Li ◽

Minfeng Chen ◽

Wei He ◽

...

Keyword(s):

Bladder Cancer ◽

Androgen Receptor ◽

Cancer Cells ◽

Cancer Growth ◽

Invasion And Migration ◽

Non Coding Rna ◽

Bladder Cancer Cells ◽

And Migration ◽

Cancer Tissues ◽

Long Non Coding Rna

Backgrounds/Aims: Long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is involved in the progression of several tumors. The interaction between lncRNA and miRNA or miRNA’s target genes is reported to play crucial roles in malignancy. In addition, Androgen receptor (AR) is considered to be involved in bladder cancer progression. In this study, we investigated the role of XIST in human bladder cancer and its interaction with miR-124 and AR. Methods: XIST and AR expression was detected in bladder tumor samples and cell lines. Effects of XIST and AR on bladder cancer cells growth, invasion and migration were analyzed. Bioinformatic analysis and luciferase assays were used to identify the interaction among XIST, AR and miR-124. The correlations of miR-124 with XIST and AR in bladder cancer samples were statistically analyzed. Results: XIST and AR were upregulated in bladder cancer tissues and positively correlated. Higher XIST and AR expression were related to poorer TNM stage of bladder cancer. XIST knockdown reduced bladder cancer cells’ proliferation, invasion and migration. While this inhibitory effect could be partially restored by AR overexpression. XIST inhibited miR-124 expression by directly targeting. Moreover, miR-124 could bind to the 3’UTR of AR to regulate its expression. MiR-124 inhibition partially restored the XIST knockdown-induced reduction of AR, c-myc, p27, MMP13 and MMP9 expression. In bladder cancer tissues, miR-124 level was inversely correlated with the expression of XIST and AR, respectively. Conclusion: These findings indicated that XIST might be an oncogenic lncRNA that promoted the bladder cancer growth, invasion and migration via miR-124 dependent AR regulation.

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Safety and efficacy of temsirolimus as second-line treatment for patients with recurrent bladder cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.7_suppl.304 ◽

2015 ◽

Vol 33 (7_suppl) ◽

pp. 304-304 ◽

Cited By ~ 2

Author(s):

Nadine Houede ◽

Guilhem Roubaud ◽

Hakim Mahammedi ◽

Lionel Vedrine ◽

Florence Joly ◽

...

Keyword(s):

Bladder Cancer ◽

Mammalian Target Of Rapamycin ◽

Signalling Pathway ◽

Weekly Dose ◽

Second Line ◽

Mutational Status ◽

Urothelial Tumors ◽

Chemotherapy Efficacy ◽

Mtor Signalling ◽

Line Chemotherapy

304 Background: Bladder cancer is the 7th cause of death from cancer in men and 10th in women. For metastatic patients, prognosis is poor with a median overall survival of 15 months that remained unchanged for the past 15 years. No standard second-line chemotherapy is available for patients who relapse. Acquired mutations leading to a deregulation of the PI3K/AKT/mTOR pathway have been reported in more than 40% of bladder cancers suggesting the use of the mTOR (mammalian target of rapamycin) signalling pathway as an attractive target for the treatment of urothelial tumors. Methods: The main objective of this study was to assess the efficacy of temsirolimus, an mTOR inhibitor that is already used for the treatment of renal cancers, in patients with recurrent or metastatic bladder cancer who already received a first line chemotherapy. Efficacy was measured in terms of non-progression of the disease at two months of treatment following the RECIST v1.1 criteria. Based on a two-stage optimal Simon’s design, a total of 15 non-progressions out of 51 eligible and assessable patients were required to claim efficacy. Patients were treated at a weekly dose of 25 mg until progression, unacceptable toxicities or withdrawal. Results: Fifty-four patients were enrolled in the study between November 2009 and July 2014 in seven French centres. At the end of the first stage, six patients out of 17 were progression-free at 2 months leading to the inclusion of additional 37 patients in the second stage of the study. Thirty-six patients were eligible and assessable for the primary efficacy endpoint. A total of 18 (50%) non-progressions were observed at 2 months. Among them, partial response was documented for two patients and stable disease for 16. Twenty-five related adverse events were observed in 19 (35.2%) of the patients. Conclusions: Our study is providing the first clinical evidence of a potential benefit of temsirolimus for the treatment of relapsed bladder cancers. Ancillary study is ongoing to investigate the mutational status of genes which are involved in the PI3K/AKT/mTOR signalling pathway in order to identify a predictive signature of response to temsirolimus in bladder cancer. Clinical trial information: NCT0187943NCT0187943.

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