ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022
Exploiting the tumor-suppressive activity of the androgen receptor by CDK4/6 inhibition in castration-resistant prostate cancer.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed.
- Genome-wide chromatin profiling reveals a nonlimiting role for RXR in macrophage-like cells stimulated with multiple nuclear receptor agonists.The Journal of biological chemistry · 2026Article
- Alterations in AR-FOXA1 signaling in prostate cancer progression and therapeutic resistance.Journal of the National Cancer Center · 2026Review
- Emerging therapies to overcome antiandrogen resistance and beyond in lethal prostate cancer.Journal of the National Cancer Center · 2026Review
- Induction of cellular senescence by androgen receptor agonist or antagonist is mediated via two novel common DYRK1A-DREAM and cyclin G2 signaling pathways in castration-resistant prostate cancer.Journal of advanced research · 2026Article
- The Novel Direct AR Target Gene Annexin A2 Mediates Androgen-Induced Cellular Senescence in Prostate Cancer Cells.Biochemical genetics · 2025Article
- Synergistic targeting strategies for prostate cancer.Nature reviews. Urology · 2025Review
- Heterogeneous Responses to High-Dose Testosterone in Castration-Resistant Prostate Cancer Tumors with Mixed Rb-Proficient and Rb-Deficient Cells.Molecular cancer therapeutics · 2025Article
- The lncRNAs PART1 and ADAMTS9-AS2 act in an antithetic manner on AR signaling and induction of cellular senescence in prostate cancer cells.International journal of surgery (London, England) · 2025Article
- Article
- Review
- Dysregulated LINC01133 expression in laryngeal carcinoma: Prognostic implications and predicted ceRNA interactome.Molecular biology research communications · 2025Article
- Canonical androgen response element motifs are tumor suppressive regulatory elements in the prostate.Nature communications · 2024Article
- Functional circuits of LYL1 controlled by supraphysiological androgen in prostate cancer cells to regulate cell senescence.Cell communication and signaling : CCS · 2024Article
- Systematic Multi-Omics Investigation of Androgen Receptor Driven Gene Expression and Epigenetics changes in Prostate Cancer.bioRxiv : the preprint server for biology · 2024Article
- The clock gene BHLHE40 and atypical CCNG2 control androgen-induced cellular senescence as a novel tumor suppressive pathway in prostate cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- Retinoblastoma-associated protein is important for TRIM24-mediated activation of the mTOR signaling pathway through DUSP2 action in prostate cancer.Cell death and differentiation · 2024Article
- Identification of Molecular Subtype and Prognostic Signature for Prostate Adenocarcinoma based on Neutrophil Extracellular Traps.Journal of Cancer · 2024Article
- Targeting CBX3 with a Dual BET/PLK1 Inhibitor Enhances the Antitumor Efficacy of CDK4/6 Inhibitors in Prostate Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Supraphysiological Androgens Promote the Tumor Suppressive Activity of the Androgen Receptor through cMYC Repression and Recruitment of the DREAM Complex.Cancer research · 2023Article
- LSD1 Inhibition Disrupts Super-Enhancer-Driven Oncogenic Transcriptional Programs in Castration-Resistant Prostate Cancer.Cancer research · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors.
Funding
Abstract
The androgen receptor (AR) plays a pivotal role in driving prostate cancer (PCa) development. However, when stimulated by high levels of androgens, AR can also function as a tumor suppressor in PCa cells. While the high-dose testosterone (high-T) treatment is currently being tested in clinical trials of castration-resistant prostate cancer (CRPC), there is still a pressing need to fully understand the underlying mechanism and thus develop treatment strategies to exploit this tumor-suppressive activity of AR. In this study, we demonstrate that retinoblastoma (Rb) family proteins play a central role in maintaining the global chromatin binding and transcriptional repression program of AR and that Rb inactivation desensitizes CRPC to the high-dose testosterone treatment in vitro and in vivo. Using a series of patient-derived xenograft (PDX) CRPC models, we further show that the efficacy of high-T treatment can be fully exploited by a CDK4/6 inhibitor, which strengthens the chromatin binding of the Rb-E2F repressor complex by blocking the hyperphosphorylation of Rb proteins. Overall, our study provides strong mechanistic and preclinical evidence on further developing clinical trials to combine high-T with CDK4/6 inhibitors in treating CRPC.
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.