ArticleThe Journal of clinical investigation2019
Molecular profiling stratifies diverse phenotypes of treatment-refractory metastatic castration-resistant prostate cancer.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 325 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.
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Who cites it
325 citing papers in PubMed, 447 citations in OpenAlex.
- Single-cell imaging analysis, therapeutic modeling and a Phase Ib trial validate BCL-2 as a target across heterogeneous castration-resistant prostate cancer.Signal transduction and targeted therapy · 2026Trial
- Single-cell and spatial RNA sequencing in prostate cancer.Nature reviews. Urology · 2026Review
- Neuromedin U 'innervation' reprograms myeloid immunosuppression in neuroendocrine prostate cancer.Oncogene · 2026Article
- Combined BET bromodomain and DNA methyltransferase inhibition targets critical survival pathways in transdifferentiated prostate cancer.JCI insight · 2026Article
- Targeting the Androgen Receptor and Associated Cofactors in Prostate Cancer: Novel Approaches and Future Perspectives.International journal of molecular sciences · 2026Review
- The RNA cargo of plasma-derived extracellular vesicles in mCRPC patients captures cancer cells and tumor microenvironment signals.bioRxiv : the preprint server for biology · 2026Article
- TMEM59L promotes neuroendocrine differentiation and enzalutamide resistance in prostate cancer by regulating MUC1/β-catenin/MYC axis.Clinical and translational medicine · 2026Article
- DLL3-Targeted Strategies in Advanced Prostate Cancer: Current Evidence and Future Perspectives.Drugs · 2026Review
- IRE1 activity is prognostic in localised and metastatic prostate cancer and affects epithelial lineage states.EMBO molecular medicine · 2026Article
- Increasing Cancer Stemness Drives Prostate Cancer Progression, Plasticity, Therapy Resistance and Poor Patient Survival.bioRxiv : the preprint server for biology · 2026Article
- Genotoxic antibody-drug conjugates combined with BCL-XL inhibitors enhance therapeutic efficacy in metastatic castration-resistant prostate cancer.The Journal of clinical investigation · 2026Article
- The Great Escape: the systems biology of endocrine resistance and lineage plasticity.Endocrine-related cancer · 2026Review
- Systematic analysis of hippo pathway signaling identifies TEAD1 as a transcriptional regulator of neuroendocrine prostate cancer.Neoplasia (New York, N.Y.) · 2026Article
- A forward genetic screen identifies Sirtuin1 as a driver of neuroendocrine prostate cancer.The Journal of experimental medicine · 2026Article
- Glutamate Ionotropic Kainate Receptors as Therapeutic Targets in Enzalutamide-Resistant and Neuroendocrine Prostate Cancer.International journal of molecular sciences · 2026Article
- Natural Products in Prostate Cancer: Crosstalk Among the Gut Microbiome, Androgen Receptor Signaling, and Epigenetic Regulation.International journal of molecular sciences · 2026Review
- Molecular insights into DDX3X-androgen receptor mRNA regulation via non-canonical G-quadruplex in castration-resistant prostate cancer.Oncogene · 2026Article
- A MYC family switch: L-MYC drives and maintains neuroendocrine lineage programs in prostate cancer.Neoplasia (New York, N.Y.) · 2026Article
- Mapping prostate cancer pathobiology: A review of genetically engineered mouse models (GEMMs).Gene · 2026Review
- Genomic Determinants of Lethality and Therapeutic Vulnerability in Castration-Resistant Prostate Cancer.bioRxiv : the preprint server for biology · 2026Article
265 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 4 institutions in 1 country.
Funding
Abstract
Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease with diverse drivers of disease progression and mechanisms of therapeutic resistance. We conducted deep phenotypic characterization of CRPC metastases and patient-derived xenograft (PDX) lines using whole genome RNA sequencing, gene set enrichment analysis and immunohistochemistry. Our analyses revealed five mCRPC phenotypes based on the expression of well-characterized androgen receptor (AR) or neuroendocrine (NE) genes: (i) AR-high tumors (ARPC), (ii) AR-low tumors (ARLPC), (iii) amphicrine tumors composed of cells co-expressing AR and NE genes (AMPC), (iv) double-negative tumors (i.e. AR-/NE-; DNPC) and (v) tumors with small cell or NE gene expression without AR activity (SCNPC). RE1-silencing transcription factor (REST) activity, which suppresses NE gene expression, was lost in AMPC and SCNPC PDX models. However, knockdown of REST in cell lines revealed that attenuated REST activity drives the AMPC phenotype but is not sufficient for SCNPC conversion. We also identified a subtype of DNPC tumors with squamous differentiation and generated an encompassing 26-gene transcriptional signature that distinguished the five mCRPC phenotypes. Together, our data highlight the central role of AR and REST in classifying treatment-resistant mCRPC phenotypes. These molecular classifications could potentially guide future therapeutic studies and clinical trial design.
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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 Socratic graph.