ArticleJCI insight2023
Reversible epigenetic alterations mediate PSMA expression heterogeneity in advanced metastatic prostate cancer.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 76 citations in OpenAlex.
- Evaluation of the safety and efficacy ofEuropean radiology experimental · 2026Trial
- Lutetium-177-PSMA-617 or cabazitaxel in metastatic prostate cancer: circulating tumor DNA analysis of the randomized phase 2 TheraP trial.Nature medicine · 2025Trial
- Longitudinally Monitoring Prostate Cancer Bone Metastasis and Treatment Response via Circulating Extracellular Vesicles.Journal of extracellular vesicles · 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
- Development of Radioligand Therapy-Responsive Syngeneic Prostate Models through Murine Prostate-Specific Membrane Antigen Point Mutation.ACS pharmacology & translational science · 2026Article
- Low-PSMA hormone-sensitive prostate cancer: a distinct clinical and molecular state.Molecular medicine (Cambridge, Mass.) · 2026Article
- Article
- Prostate‑specific membrane antigen: Molecular functions and emerging roles as a therapeutic target (Review).Molecular medicine reports · 2026Review
- Pan-cancer analysis reveals FOLH1 as a prognostic biomarker and immune modulator in human tumors.Translational cancer research · 2026Article
- EpCAM-PSMA: Potential predictors of treatment outcomes for PSMA-targeted alpha therapies in metastatic castration-resistant prostate cancer.Molecular therapy. Oncology · 2026Article
- Comparative evaluation of [¹⁸F]FAPI-42 and [¹⁸F]PSMA-1007 PET/CT for lesion detection and uptake in prostate cancer across disease stages.EJNMMI research · 2026Article
- Cell surface oncofetal antigens in prostate cancer: therapeutic potential and radioligand targeting.EJNMMI research · 2026Review
- Focusing on Prostate-Specific Membrane Antigen in Precision Diagnosis and Treatment of Prostate Cancer.Biomedicines · 2026Review
- Harnessing Folate-Mediated PSMA Targeting for Precision Therapy: An Intelligent Liposomal Nanoplatform Against Prostate Cancer.Pharmaceutics · 2026Article
- Variable cellular and radiobiological effects of [Journal of experimental & clinical cancer research : CR · 2026Article
- Genetic and epigenetic mechanisms underlying treatment-induced neuroendocrine prostate cancer.Journal of the National Cancer Center · 2026Review
- Magnetically Navigated and PSMA/STEAP1 Dual-Targeted Nanoliposomes for NIR-II/MRI Imaging with Photothermal-Chemo-Immunotherapy for Prostate Cancer.Research (Washington, D.C.) · 2026Article
- Engineering Multimodal Nanomaterials for Prostate Cancer Theranostics: Design Principles, Recent Advances, and Translational Challenges.International journal of nanomedicine · 2026Review
- Trop2 immuno-PET/CT imaging of prostate cancer: a proof-of-concept translational study.BMC medicine · 2025Article
- Intratumoral Heterogeneity of MAGED4 Expression in Oral Squamous Cell Carcinoma: Epigenetic Mechanisms and Therapeutic Implications.International journal of molecular sciences · 2025Article
Corrections and comments
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Authors and funding
25 authors at 5 institutions in 1 country.
Funding
Abstract
Prostate-specific membrane antigen (PSMA) is an important cell surface target in prostate cancer. There are limited data on the heterogeneity of PSMA tissue expression in metastatic castration-resistant prostate cancer (mCRPC). Furthermore, the mechanisms regulating PSMA expression (encoded by the FOLH1 gene) are not well understood. Here, we demonstrate that PSMA expression is heterogeneous across different metastatic sites and molecular subtypes of mCRPC. In a rapid autopsy cohort in which multiple metastatic sites per patient were sampled, we found that 13 of 52 (25%) cases had no detectable PSMA and 23 of 52 (44%) cases showed heterogeneous PSMA expression across individual metastases, with 33 (63%) cases harboring at least 1 PSMA-negative site. PSMA-negative tumors displayed distinct transcriptional profiles with expression of druggable targets such as MUC1. Loss of PSMA was associated with epigenetic changes of the FOLH1 locus, including gain of CpG methylation and loss of histone 3 lysine 27 (H3K27) acetylation. Treatment with histone deacetylase (HDAC) inhibitors reversed this epigenetic repression and restored PSMA expression in vitro and in vivo. Collectively, these data provide insights into the expression patterns and regulation of PSMA in mCRPC and suggest that epigenetic therapies - in particular, HDAC inhibitors - can be used to augment PSMA levels.
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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.