Evidence map›Paper›PMID 40118049›Full record

ArticleCancer cell2025

Small-molecule RNA therapeutics to target prostate cancer.

Duygu Kuzuoglu-Ozturk, Hao G Nguyen, Lingru Xue, Emma Figueredo, Vishvak Subramanyam, Isabelle Liu, Kenya Bonitto, Ashish Noronha, Adrianna Dabrowska, Janet E Cowan and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed.

  1. A conserved eIF1ACell reports. Medicine · 2026
    Trial
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. DHX37 and tumor growth: a novel avenue for melanoma research.Journal of translational medicine · 2026
    Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Duygu Kuzuoglu-OzturkDepartment of Urology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA; Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul, Turkey.
Hao G NguyenDepartment of Urology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA. Electronic address: hao.nguyen@ucsf.edu.
Lingru XueDepartment of Urology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Emma FigueredoDepartment of Urology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Vishvak SubramanyamDepartment of Urology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA; Department of Biochemistry & Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Isabelle LiuDepartment of Urology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA; Department of Biochemistry & Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Kenya BonittoDepartment of Urology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA; Tetrad Graduate Program, University of California, San Francisco, CA, USA.
Ashish NoronhaDepartment of Urology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Adrianna DabrowskaDepartment of Urology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Janet E CowanDepartment of Urology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Juan A Oses-PrietoDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
Alma L BurlingameDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
Stephen T WorlandeFFECTOR Therapeutics, San Diego, USA.
Peter R CarrollDepartment of Urology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Davide RuggeroDepartment of Urology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA. Electronic address: davide.ruggero@ucsf.edu.

Funding

Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Alan Ashworth · 1999 to 2026
$209.7M
UCSF Specialized Programs of Research Excellence (SPOREs) in Prostate CancerP50CA275741 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ERIC J SMALL · 2024 to 2026
$8.8M
Mechanisms of regulated translation control in cancer and its therapeutic implicationsR35CA242986 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RUGGERO, DAVIDE · 2019 to 2025
$6.4M
MELT: Modulation of PSMA Expression for Lutetium TherapyR01CA235741 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HOPE, THOMAS A · 2019 to 2025
$3.2M
Illumina NovaSeq 6000 Sequencing SystemS10OD028511 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHOW, ERIC D · 2020 to 2020
$583k
NCI NIH HHS P30 CA082103NCI NIH HHS P50 CA275741NCI NIH HHS R01 CA235741NCI NIH HHS R35 CA242986NIH HHS S10 OD028511
6 · The paper itself

Abstract

Tuning protein expression by targeting RNA structure using small molecules is an unexplored avenue for cancer treatment. To understand whether this vulnerability could be therapeutically targeted in the most lethal form of prostate cancer, castration-resistant prostate cancer (CRPC), we use a clinical small molecule, zotatifin, that targets the RNA helicase and translation factor eukaryotic initiation factor 4A (eIF4A). Zotatifin represses tumorigenesis in patient-derived and xenograft models and prolonged survival in vivo alongside hormone therapy. Genome-wide transcriptome, translatome, and proteomic analysis reveals two important translational targets: androgen receptor (AR), a key oncogene in CRPC, and hypoxia-inducible factor 1A (HIF1A), an essential cancer modulator in hypoxia. We solve the structure of the 5' UTRs of these oncogenic mRNAs and strikingly observe complex structural remodeling of these select mRNAs by this small molecule. Remarkably, tumors treated with zotatifin become more sensitive to anti-androgen therapy and radiotherapy. Therefore, "translatome therapy" provides additional strategies to treat the deadliest cancers.

Indexed as

Prostatic NeoplasmsProstatic Neoplasms, Castration-ResistantThiohydantoins5' Untranslated RegionsAnimalsCell Line, TumorEukaryotic Initiation Factor-4AGene Expression Regulation, NeoplasticHumansHypoxia-Inducible Factor 1, alpha SubunitMaleMiceReceptors, AndrogenRNA, MessengerXenograft Model Antitumor Assays5' Untranslated RegionsAR protein, humanEukaryotic Initiation Factor-4AHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitReceptors, AndrogenRNA, MessengerThiohydantoins5′ UTRARcombinational therapyeIF4AHIF1AmCRPCprostate cancerRNA structuretranslational controlzotatifin

Identifiers

PMID40118049
PMCPMC12124822

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.