ArticleNature medicine2016
Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer.
Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 1,130 papers.
What it found
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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.
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.
A Randomized Phase II Trial Comparing Biomarker Directed Therapy Versus Clinician's Choice of Enzalutamide or Docetaxel in Patients With Advanced Prostate Cancer Post Abiraterone
5-Alpha Reductase 2 as a Marker of Resistance to 5ARI Therapy
In Situ Clonal Heterogeneity in Prostatic Diagnostic Biopsies: Impact on Prostate Cancer Evolution and Clinical Outcome. A Retrospective, Proof of Concept Study
Who cites it
1,130 citing papers in PubMed, 1,701 citations in OpenAlex.
- Phase 2 study of talabostat, a small molecule inhibitor of dipeptidyl peptidases (DPP), administered in combination with pembrolizumab in patients with small cell neuroendocrine prostate cancer.Journal for immunotherapy of cancer · 2026Trial
- Whole genome sequencing of 378 prostate cancer metastases reveals tissue selectivity for mismatch deficiency with potential therapeutic implications.Genome medicine · 2025Trial
- Article
- Epigenetic reprogramming of lineage switching in cancer.FEBS letters · 2026Review
- Single-cell and spatial RNA sequencing in prostate cancer.Nature reviews. Urology · 2026Review
- IRE1 activity is prognostic in localised and metastatic prostate cancer and affects epithelial lineage states.EMBO molecular medicine · 2026Article
- Combined BET bromodomain and DNA methyltransferase inhibition targets critical survival pathways in transdifferentiated prostate cancer.JCI insight · 2026Article
- Article
- Castration-resistant prostate cancer as an adaptive tumor ecosystem: coupling tumor evolution with microenvironmental reprogramming.Cancer metastasis reviews · 2026Review
- PAX5 modulates vascularization and contributes to neuroendocrine lineage transition during carcinoma progression.The Journal of clinical investigation · 2026Article
- A stress-adaptive lipid kinase axis defines metabolic vulnerabilities in neuroendocrine prostate cancer.Cancer cell · 2026Article
- ATP-dependent chromatin remodelers in prostate cancer progression and therapeutic resistance.Endocrinology · 2026Review
- Castration-resistant prostate cancer cells are addicted to the high activity of cyclin-dependent kinase 2.Molecular oncology · 2026Article
- Article
- Vitronectin Enrichment in Prostate Cancer Liver Metastases Promotes Adhesion and Survival.Cancer research communications · 2026Article
- Urinary Biomarkers in Urological Oncology: From Biological Origin to Clinical Decision-Making-A Narrative Review.Diagnostics (Basel, Switzerland) · 2026Review
- TMEM59L promotes neuroendocrine differentiation and enzalutamide resistance in prostate cancer by regulating MUC1/β-catenin/MYC axis.Clinical and translational medicine · 2026Article
- Cancer Neuroscience: From Local Neuro-Immune Microenvironments to Systemic Brain-Body Circuitry.MedComm · 2026Review
- HO-1 Nuclear Interactome Implications in Neuroendocrine Transdifferentiation in Prostate Cancer.International journal of molecular sciences · 2026Article
- Increasing Cancer Stemness Drives Prostate Cancer Progression, Plasticity, Therapy Resistance and Poor Patient Survival.bioRxiv : the preprint server for biology · 2026Article
1,070 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 3 countries.
Funding
Abstract
An increasingly recognized resistance mechanism to androgen receptor (AR)-directed therapy in prostate cancer involves epithelial plasticity, in which tumor cells demonstrate low to absent AR expression and often have neuroendocrine features. The etiology and molecular basis for this 'alternative' treatment-resistant cell state remain incompletely understood. Here, by analyzing whole-exome sequencing data of metastatic biopsies from patients, we observed substantial genomic overlap between castration-resistant tumors that were histologically characterized as prostate adenocarcinomas (CRPC-Adeno) and neuroendocrine prostate cancer (CRPC-NE); analysis of biopsy samples from the same individuals over time points to a model most consistent with divergent clonal evolution. Genome-wide DNA methylation analysis revealed marked epigenetic differences between CRPC-NE tumors and CRPC-Adeno, and also designated samples of CRPC-Adeno with clinical features of AR independence as CRPC-NE, suggesting that epigenetic modifiers may play a role in the induction and/or maintenance of this treatment-resistant state. This study supports the emergence of an alternative, 'AR-indifferent' cell state through divergent clonal evolution as a mechanism of treatment resistance in advanced prostate cancer.
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What OpenQuestion holds
Registered trials
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.