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Identifying prognostic targets in metastatic prostate cancer beyond AR

Feng, Emily ; Feng, Eric ; Berg, Tracy LU ; Nguyen, Isabella S. ; Nguyen, Lilac G. ; Chen, William ; Zhang, Meng ; Quigley, David ; Sharifi, Marina and Li, Haolong , et al. (2025) In FEBS Open Bio
Abstract

Genome-wide screens using CRISPR/RNAi can identify new therapeutic vulnerabilities in prostate cancer. In this study, we combine DepMap functional screen data with a large gene expression database (N = 1012) and clinical outcomes to identify potentially druggable targets. Eight genes (CYC, CYP51A1, DHFR, EBP, KIF15, PPM1D, SQLE, and UMPS) demonstrated strong dependency in cell lines and were also associated with worse prognosis clinically, representing potential therapeutic targets in metastatic prostate cancer. Four of these (DHFR, EBP, KIF15, and PPM1D) demonstrated higher expression in neuroendocrine prostate cancer. Furthermore, all but one (KIF15) were not significantly decreased from pretreatment to posttreatment, suggesting that... (More)

Genome-wide screens using CRISPR/RNAi can identify new therapeutic vulnerabilities in prostate cancer. In this study, we combine DepMap functional screen data with a large gene expression database (N = 1012) and clinical outcomes to identify potentially druggable targets. Eight genes (CYC, CYP51A1, DHFR, EBP, KIF15, PPM1D, SQLE, and UMPS) demonstrated strong dependency in cell lines and were also associated with worse prognosis clinically, representing potential therapeutic targets in metastatic prostate cancer. Four of these (DHFR, EBP, KIF15, and PPM1D) demonstrated higher expression in neuroendocrine prostate cancer. Furthermore, all but one (KIF15) were not significantly decreased from pretreatment to posttreatment, suggesting that they may remain targetable postabiraterone therapy. All eight genes showed evidence of protein expression in prostate cancers or cell lines. These potentially druggable targets associated with prostate cancer cell line dependency and worse clinical outcomes have also demonstrated literature support as potential targets, supporting further research into their potential clinical relevance as therapeutic targets in prostate cancer.

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type
Contribution to journal
publication status
epub
subject
keywords
clinicogenomic, DepMap, prostate cancer
in
FEBS Open Bio
publisher
Wiley-Blackwell
external identifiers
  • pmid:40405591
  • scopus:105006692129
ISSN
2211-5463
DOI
10.1002/2211-5463.70059
language
English
LU publication?
yes
id
df723da5-fd0a-4368-b27c-f625220f0f97
date added to LUP
2025-09-19 11:51:19
date last changed
2025-09-19 12:56:29
@article{df723da5-fd0a-4368-b27c-f625220f0f97,
  abstract     = {{<p>Genome-wide screens using CRISPR/RNAi can identify new therapeutic vulnerabilities in prostate cancer. In this study, we combine DepMap functional screen data with a large gene expression database (N = 1012) and clinical outcomes to identify potentially druggable targets. Eight genes (CYC, CYP51A1, DHFR, EBP, KIF15, PPM1D, SQLE, and UMPS) demonstrated strong dependency in cell lines and were also associated with worse prognosis clinically, representing potential therapeutic targets in metastatic prostate cancer. Four of these (DHFR, EBP, KIF15, and PPM1D) demonstrated higher expression in neuroendocrine prostate cancer. Furthermore, all but one (KIF15) were not significantly decreased from pretreatment to posttreatment, suggesting that they may remain targetable postabiraterone therapy. All eight genes showed evidence of protein expression in prostate cancers or cell lines. These potentially druggable targets associated with prostate cancer cell line dependency and worse clinical outcomes have also demonstrated literature support as potential targets, supporting further research into their potential clinical relevance as therapeutic targets in prostate cancer.</p>}},
  author       = {{Feng, Emily and Feng, Eric and Berg, Tracy and Nguyen, Isabella S. and Nguyen, Lilac G. and Chen, William and Zhang, Meng and Quigley, David and Sharifi, Marina and Li, Haolong and Coleman, Ilsa and Nelson, Peter S. and Sjöström, Martin and Zhao, Shuang G.}},
  issn         = {{2211-5463}},
  keywords     = {{clinicogenomic; DepMap; prostate cancer}},
  language     = {{eng}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{FEBS Open Bio}},
  title        = {{Identifying prognostic targets in metastatic prostate cancer beyond AR}},
  url          = {{http://dx.doi.org/10.1002/2211-5463.70059}},
  doi          = {{10.1002/2211-5463.70059}},
  year         = {{2025}},
}