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Record W3024601170 · doi:10.1073/pnas.1922207117

Transcriptional profiling identifies an androgen receptor activity-low, stemness program associated with enzalutamide resistance

2020· article· en· W3024601170 on OpenAlex
Joshi J. Alumkal, Duanchen Sun, Eric Lu, Tomasz M. Beer, George Thomas, Emile Latour, Rahul Aggarwal, Jeremy Cetnar, Charles J. Ryan, Shaadi Tabatabaei, Shawna Bailey, Claire B. Turina, David A. Quigley, Xiangnan Guan, Adam Foye, Jack Youngren, Joshua A. Urrutia, Jiaoti Huang, Alana S. Weinstein, Verena Friedl, Matthew B. Rettig, Robert E. Reiter, Daniel E. Spratt, Martin Gleave, Christopher P. Evans, Joshua M. Stuart, Yiyi Chen, Felix Y. Feng, Eric J. Small, Owen N. Witte, Zheng Xia

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2020
Typearticle
Languageen
FieldMedicine
TopicProstate Cancer Treatment and Research
Canadian institutionsUniversity of British Columbia
FundersNational Cancer InstituteComprehensive Cancer Center, University of MichiganU.S. Department of DefenseStand Up To CancerJanssen BiotechAstellas PharmaUniversity of Michigan
KeywordsEnzalutamideAndrogen receptorProstate cancerCancer researchMedicineAndrogenClinical trialOncologyInternal medicineBiologyCancerHormone

Abstract

fetched live from OpenAlex

Significance The androgen receptor (AR) antagonist enzalutamide is one of the principal treatments for men with metastatic castration-resistant prostate cancer. However, not all patients respond, and de novo resistance mechanisms are largely unknown. To clarify mechanisms that contribute to enzalutamide resistance, we conducted a single-arm enzalutamide clinical trial. Metastatic tissue biopsies were required prior to study entry so we could attempt to identify molecular features associated with de novo resistance. Transcriptional profiling identified specific gene sets—including those linked to reduced AR transcriptional activity and a stemness program—that were activated in nonresponders. Our results suggest that patients whose tumors harbor this program should be considered for clinical trials testing rational agents to overcome de novo enzalutamide resistance.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.056
Threshold uncertainty score0.304

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.001
Scholarly communication0.0000.001
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.082
GPT teacher head0.354
Teacher spread0.272 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it