ArticleCancer discovery2022
Drug-Induced Epigenomic Plasticity Reprograms Circadian Rhythm Regulation to Drive Prostate Cancer toward Androgen Independence.
Article in Cancer discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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.
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
61 citing papers in PubMed, 84 citations in OpenAlex.
- Cambridge Neoadjuvant Cancer of the Prostate (CANCAP03): A Window Study into the Effects of Olaparib ± Degarelix in Primary Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Whole genome sequencing of 378 prostate cancer metastases reveals tissue selectivity for mismatch deficiency with potential therapeutic implications.Genome medicine · 2025Trial
- Temporal dynamics of the immune response to neoadjuvant androgen deprivation therapy suggest a window of opportunity for checkpoint inhibitor therapy in prostate cancer.Journal for immunotherapy of cancer · 2026Article
- Targeting the Androgen Receptor and Associated Cofactors in Prostate Cancer: Novel Approaches and Future Perspectives.International journal of molecular sciences · 2026Review
- Article
- Review
- Article
- SMARCA4 promotes lineage plasticity and enzalutamide resistance in prostate cancer by regulating PROX1 via H3K27 acetylation.Cell death discovery · 2026Article
- Targeting pre-existing club-like cells in prostate cancer potentiates androgen deprivation therapy.EMBO molecular medicine · 2026Article
- Alterations in AR-FOXA1 signaling in prostate cancer progression and therapeutic resistance.Journal of the National Cancer Center · 2026Review
- The Circadian Rhythm Regulates the Hepato-ovarian Axis Linking Polycystic Ovary Syndrome and Non-alcoholic Fatty Liver Disease.Biochemical genetics · 2026Article
- ZFP42 maintains stemness and rhythmic transcription in human epidermal stem and progenitor cells via CRY1.Communications biology · 2026Article
- Primary Cilium Forces Neuroendocrine Shift in Prostate Cancer through YAP1 Repression and Reduced Mitochondrial Activity.Theranostics · 2026Article
- ZDHHC2-Dependent Palmitoylation Dictates Ferroptosis and Castration Sensitivity in Prostate Cancer via Controlling ACSL4 Degradation and Lipid Peroxidation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Circadian clock and cancer.Military Medical Research · 2026Review
- Review
- Circadian regulator REV-ERBα is a master regulator of tumor lineage plasticity and an effective therapeutic target.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Increased ErbB2 Signaling Is an Early Adaptation to Androgen Signaling Inhibition and Persists in Castration-Resistant Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Enzalutamide-Resistant STEAP4Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Germline-Somatic Liaison Dictates Cancer Subtypes via de novo Steroid Biosynthesis.Cancer discovery · 2025Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
36 authors at 10 institutions in 5 countries.
Funding
Abstract
In prostate cancer, androgen receptor (AR)-targeting agents are very effective in various disease stages. However, therapy resistance inevitably occurs, and little is known about how tumor cells adapt to bypass AR suppression. Here, we performed integrative multiomics analyses on tissues isolated before and after 3 months of AR-targeting enzalutamide monotherapy from patients with high-risk prostate cancer enrolled in a neoadjuvant clinical trial. Transcriptomic analyses demonstrated that AR inhibition drove tumors toward a neuroendocrine-like disease state. Additionally, epigenomic profiling revealed massive enzalutamide-induced reprogramming of pioneer factor FOXA1 from inactive chromatin sites toward active cis-regulatory elements that dictate prosurvival signals. Notably, treatment-induced FOXA1 sites were enriched for the circadian clock component ARNTL. Posttreatment ARNTL levels were associated with patients' clinical outcomes, and ARNTL knockout strongly decreased prostate cancer cell growth. Our data highlight a remarkable cistromic plasticity of FOXA1 following AR-targeted therapy and revealed an acquired dependency on the circadian regulator ARNTL, a novel candidate therapeutic target. SIGNIFICANCE: Understanding how prostate cancers adapt to AR-targeted interventions is critical for identifying novel drug targets to improve the clinical management of treatment-resistant disease. Our study revealed an enzalutamide-induced epigenomic plasticity toward prosurvival signaling and uncovered the circadian regulator ARNTL as an acquired vulnerability after AR inhibition, presenting a novel lead for therapeutic development. See related commentary by Zhang et al., p. 2017. This article is highlighted in the In This Issue feature, p. 2007.
Indexed as
Identifiers
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.