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A Preclinical Study to Repurpose Spironolactone for Enhancing Chemotherapy Response in Bladder Cancer

Overview of attention for article published in Molecular Cancer Therapeutics, February 2022
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3 tweeters

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1 Mendeley
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Title
A Preclinical Study to Repurpose Spironolactone for Enhancing Chemotherapy Response in Bladder Cancer
Published in
Molecular Cancer Therapeutics, February 2022
DOI 10.1158/1535-7163.mct-21-0613
Pubmed ID
Authors

Dongbo Xu, Qiang Cao, Li Wang, Jianmin Wang, Bo Xu, Kristopher Attwood, Lei Wei, Yue Wu, Gary J. Smith, Eriko Katsuta, Kazuaki Takabe, Gurkamal Chatta, Khurshid A. Guru, David W. Goodrich, Qiang J. Li

Abstract

Neoadjuvant chemotherapy (NAC) followed by radical cystectomy is the standard of care for patients with muscle-invasive bladder cancer (MIBC). Defects in nucleotide excision repair (NER) are associated with improved responses to NAC. Excision Repair Cross-Complementation group 3 (ERCC3) is a key component of NER process. No NER inhibitors are available for treating bladder cancer patients. We have developed an ex vivo cell-based assay of 6-4 pyrimidine-pyrimidinone (6-4PP) removal as a surrogate measure of NER capacity in human bladder cancer cell lines. The protein expression of ERCC3 was examined in human MIBC specimens and cell lines. Small molecule inhibitors were screened for NER inhibition in bladder cancer cell lines. Spironolactone (SP) was identified as a potent NER inhibitor. Combined effects of SP with chemo-drugs were evaluated in vitro and in vivo. The efficacy between platinum and SP on cytotoxicity was determined by combination index. A correlation between NER capacity and cisplatin sensitivity was demonstrated in a series of bladder cancer cell lines. Further, siRNA-mediated knockdown of ERCC3 abrogated NER capacity and enhanced cisplatin cytotoxicity. SP inhibited ERCC3 protein expression, abrogated NER capacity, and increased platinum-induced cytotoxicity in bladder cancer cells in vivo and in patient-derived organoids. Moreover, SP exhibited the potential synergism effects with other clinical chemotherapy regimens in bladder cancer cell lines. Our data support the notion of re-purposing SP for improving the chemotherapy response of NAC in MIBC patients. Further clinical trials are warranted to determine the safety and efficacy of SP in combination with chemotherapy.

Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 1 Mendeley reader of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 1 100%

Demographic breakdown

Readers by professional status Count As %
Professor > Associate Professor 1 100%
Readers by discipline Count As %
Medicine and Dentistry 1 100%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 May 2022.
All research outputs
#13,885,794
of 21,399,109 outputs
Outputs from Molecular Cancer Therapeutics
#2,787
of 3,699 outputs
Outputs of similar age
#180,258
of 337,014 outputs
Outputs of similar age from Molecular Cancer Therapeutics
#27
of 37 outputs
Altmetric has tracked 21,399,109 research outputs across all sources so far. This one is in the 33rd percentile – i.e., 33% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,699 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.9. This one is in the 22nd percentile – i.e., 22% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 337,014 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 43rd percentile – i.e., 43% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 37 others from the same source and published within six weeks on either side of this one. This one is in the 27th percentile – i.e., 27% of its contemporaries scored the same or lower than it.