Evidence map›Paper›PMID 34322653›Full record

Trial reportJCO precision oncology2021

Loss of

Marek Cmero, Natalie J Kurganovs, Ryan Stuchbery, Patrick McCoy, Corrina Grima, Anne Ngyuen, Ken Chow, Stefano Mangiola, Geoff Macintyre, Nicholas Howard and 12 more

Open access · hybridAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in JCO precision oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.8field-weighted citation impact, top 14% of its field
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

14 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. EMT and cancer: what clinicians should know.Nature reviews. Clinical oncology · 2025
    Review
  3. Article
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  5. 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

22 authors at 6 institutions in 2 countries.

Marek CmeroDepartment of Surgery, University of Melbourne, Parkville, Victoria, Australia.
Natalie J KurganovsDepartment of Surgery, University of Melbourne, Parkville, Victoria, Australia.
Ryan StuchberyDepartment of Surgery, University of Melbourne, Parkville, Victoria, Australia.
Patrick McCoyDepartment of Surgery, University of Melbourne, Parkville, Victoria, Australia.
Corrina GrimaDepartment of Surgery, University of Melbourne, Parkville, Victoria, Australia.
Anne NgyuenDepartment of Surgery, University of Melbourne, Parkville, Victoria, Australia.
Ken ChowDepartment of Surgery, University of Melbourne, Parkville, Victoria, Australia.
Stefano MangiolaDepartment of Surgery, University of Melbourne, Parkville, Victoria, Australia.
Geoff MacintyreCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.
Nicholas HowardDepartment of Urology, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Michael KergerDepartment of Urology, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Philip DundeeDepartment of Urology, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Paul RuljancichDepartment of Urology, Box Hill Hospital, Box Hill, Victoria, Australia.
David ClarkeDepartment of Urology, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Jeremy GrummetDepartment of Urology, Alfred Hospital, Prahan, Victoria, Australia.
Justin S PetersDepartment of Urology, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Anthony J CostelloDepartment of Surgery, University of Melbourne, Parkville, Victoria, Australia.
Sam NordenTissuPath, Mount Waverly, Victoria, Australia.
Andrew RyanTissuPath, Mount Waverly, Victoria, Australia.
Phillip ParenteMonash University, Clayton, Victoria, Australia.
Christopher M HovensDepartment of Surgery, University of Melbourne, Parkville, Victoria, Australia.
Niall M CorcoranDepartment of Surgery, University of Melbourne, Parkville, Victoria, Australia.
The Royal Melbourne Hospital · AUThe University of Melbourne · AUBox Hill Hospital · AUTissuPath · AUThe Alfred Hospital · AUUniversity of Cambridge · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeAndrogen receptor (AR) signaling is important in prostate cancer progression, and therapies that target this pathway have been the mainstay of treatment for advanced disease for over 70 years. Tumors eventually progress despite castration through a number of well-characterized mechanisms; however, little is known about what determines the magnitude of response to short-term pathway inhibition.

methodsWe evaluated a novel combination of AR-targeting therapies (degarelix, abiraterone, and bicalutamide) and noted that the objective patient response to therapy was highly variable. To investigate what was driving treatment resistance in poorly responding patients, as a secondary outcome we comprehensively characterized pre- and post-treatment samples using both whole-genome and RNA sequencing.

resultsWe find that resistance following short-term treatment differs molecularly from typical progressive castration-resistant disease, associated with transcriptional reprogramming, to a transitional epithelial-to-mesenchymal transition (EMT) phenotype rather than an upregulation of AR signaling. Unexpectedly, tolerance to therapy appears to be the default state, with treatment response correlating with the prevalence of tumor cells deficient for

conclusionWe show that EMT characterizes acutely resistant prostate tumors and that deletion of

Indexed as

AgedAndrogen AntagonistsAndrostenesAnilidesAntineoplastic Agents, HormonalDrug Resistance, NeoplasmEpithelial-Mesenchymal TransitionGene Expression Regulation, NeoplasticHumansMaleNitrilesOligopeptidesProstatic Neoplasms, Castration-ResistantSignal TransductionSnail Family Transcription FactorsTosyl Compoundsabirateroneacetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamideAndrogen AntagonistsAndrostenesAnilidesAntineoplastic Agents, HormonalbicalutamideNitrilesOligopeptidesSNAI2 protein, humanSnail Family Transcription FactorsTosyl Compounds

Identifiers

PMID34322653
PMCPMC8238292
OpenAlexW3173753445

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.