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Drug-Induced Epigenomic Plasticity Reprograms Circadian Rhythm Regulation to Drive Prostate Cancer toward Androgen Independence

Overview of attention for article published in Cancer Discovery, June 2022
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (98th percentile)
  • High Attention Score compared to outputs of the same age and source (96th percentile)

Mentioned by

news
20 news outlets
blogs
2 blogs
twitter
59 tweeters
facebook
1 Facebook page

Citations

dimensions_citation
3 Dimensions

Readers on

mendeley
21 Mendeley
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Title
Drug-Induced Epigenomic Plasticity Reprograms Circadian Rhythm Regulation to Drive Prostate Cancer toward Androgen Independence
Published in
Cancer Discovery, June 2022
DOI 10.1158/2159-8290.cd-21-0576
Pubmed ID
Authors

Simon Linder, Marlous Hoogstraat, Suzan Stelloo, Nils Eickhoff, Karianne Schuurman, Hilda de Barros, Maartje Alkemade, Elise M. Bekers, Tesa M. Severson, Joyce Sanders, Chia-Chi Flora Huang, Tunc Morova, Umut Berkay Altintas, Liesbeth Hoekman, Yongsoo Kim, Sylvan C. Baca, Martin Sjöström, Anniek Zaalberg, Dorine C. Hintzen, Jeroen de Jong, Roelof J.C. Kluin, Iris de Rink, Claudia Giambartolomei, Ji-Heui Seo, Bogdan Pasaniuc, Maarten Altelaar, René H. Medema, Felix Y. Feng, Amina Zoubeidi, Matthew L. Freedman, Lodewyk F.A. Wessels, Lisa M. Butler, Nathan A. Lack, Henk van der Poel, Andries M. Bergman, Wilbert Zwart

Abstract

In prostate cancer, androgen receptor (AR)-targeting agents are very effective in various disease stages. However, therapy resistance inevitably occurs and little is known about how tumor cells adapt to bypass AR suppression. Here, we performed integrative multi-omics analyses on tissues isolated before and after 3 months of AR-targeting enzalutamide monotherapy from high-risk prostate cancer patients enrolled in a neoadjuvant clinical trial. Transcriptomic analyses demonstrated that AR inhibition drove tumors towards a neuroendocrine-like disease state. Additionally, epigenomic profiling revealed massive enzalutamide-induced reprogramming of pioneer factor FOXA1 - from inactive chromatin sites towards active cis-regulatory elements that dictate pro-survival signals. Notably, treatment-induced FOXA1 sites were enriched for circadian clock component ARNTL. Post-treatment ARNTL levels associated with poor outcome, and ARNTL knockout strongly decreased prostate cancer cell growth. Our data highlight a remarkable cistromic plasticity of FOXA1 following AR-targeted therapy, and revealed an acquired dependency on circadian regulator ARNTL, a novel candidate therapeutic target.

Twitter Demographics

The data shown below were collected from the profiles of 59 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 21 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 21 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 8 38%
Other 2 10%
Unspecified 2 10%
Student > Bachelor 2 10%
Student > Master 1 5%
Other 3 14%
Unknown 3 14%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 43%
Medicine and Dentistry 4 19%
Unspecified 2 10%
Veterinary Science and Veterinary Medicine 1 5%
Agricultural and Biological Sciences 1 5%
Other 1 5%
Unknown 3 14%

Attention Score in Context

This research output has an Altmetric Attention Score of 187. 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 26 September 2022.
All research outputs
#165,999
of 22,137,934 outputs
Outputs from Cancer Discovery
#51
of 3,541 outputs
Outputs of similar age
#4,684
of 342,262 outputs
Outputs of similar age from Cancer Discovery
#6
of 132 outputs
Altmetric has tracked 22,137,934 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,541 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 18.9. This one has done particularly well, scoring higher than 98% of its peers.
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 342,262 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 98% of its contemporaries.
We're also able to compare this research output to 132 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 96% of its contemporaries.