ArticleThe Journal of clinical investigation2023
The catalytic subunit of DNA-PK regulates transcription and splicing of AR in advanced prostate cancer.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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The trial behind it
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Who cites it
16 citing papers in PubMed, 10 citations in OpenAlex.
- Targeting the Androgen Receptor and Associated Cofactors in Prostate Cancer: Novel Approaches and Future Perspectives.International journal of molecular sciences · 2026Review
- CDK12/13 Inhibition Induces DNA Hypomethylation and Sensitizes Cancer Cells to Compounds Targeting DNA-PK.Journal of cellular and molecular medicine · 2026Article
- Targeting DNA-PK: medicinal chemistry insights into small-molecule inhibitor discovery and optimisation.RSC medicinal chemistry · 2026Review
- DNA-PKcs inhibition sensitizes glioblastoma to radiotherapy through reprogramming of tumor cell states and immune microenvironment cell types.Research square · 2026Article
- Splicing factor TRA2B enhances synthesis of androgen receptor variant AR-V7 in prostate cancer cells.The Journal of clinical investigation · 2026Article
- Androgen receptor splice variant 7 expression levels distinguish AR-mutated from nonmutated metastatic castration-resistant prostate cancers.The Journal of clinical investigation · 2026Article
- Identification of CAND1 as a DNA-dependent protein kinase-regulated coactivator of androgen receptor and the ARv7 splice variant.PloS one · 2026Article
- The interconnection between androgen receptor and DNA damage response pathways in prostate cancer.Current urology · 2025Review
- Unlocking the Therapeutic Potential of DNA-PKcs in Cancer: Comprehensive Insights into Mechanisms and Clinical Applications.Cancers · 2025Review
- A Super-Enhancer-Driven Transcriptional Regulatory Circuit Underlying Abiraterone Resistance in Castration-Resistant Prostate Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- DNA-PKcs, a player winding and dancing with RNA metabolism and diseases.Cellular & molecular biology letters · 2025Review
- Defining Splicing Factor Requirements for Androgen Receptor Variant Synthesis in Advanced Prostate Cancer.Molecular cancer research : MCR · 2024Article
- The multifaceted functions of DNA-PKcs: implications for the therapy of human diseases.MedComm · 2024Review
- RNA m6a Methylation Regulator Expression in Castration-Resistant Prostate Cancer Progression and Its Genetic Associations.Cancers · 2024Article
- Tissue-Based Diagnostic Biomarkers of Aggressive Variant Prostate Cancer: A Narrative Review.Cancers · 2024Review
- Review
Corrections and comments
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Authors and funding
22 authors at 6 institutions in 1 country.
Funding
Abstract
Aberrant androgen receptor (AR) signaling drives prostate cancer (PC), and it is a key therapeutic target. Although initially effective, the generation of alternatively spliced AR variants (AR-Vs) compromises efficacy of treatments. In contrast to full-length AR (AR-FL), AR-Vs constitutively activate androgenic signaling and are refractory to the current repertoire of AR-targeting therapies, which together drive disease progression. There is an unmet clinical need, therefore, to develop more durable PC therapies that can attenuate AR-V function. Exploiting the requirement of coregulatory proteins for AR-V function has the capacity to furnish tractable routes for attenuating persistent oncogenic AR signaling in advanced PC. DNA-PKcs regulates AR-FL transcriptional activity and is upregulated in both early and advanced PC. We hypothesized that DNA-PKcs is critical for AR-V function. Using a proximity biotinylation approach, we demonstrated that the DNA-PK holoenzyme is part of the AR-V7 interactome and is a key regulator of AR-V-mediated transcription and cell growth in models of advanced PC. Crucially, we provide evidence that DNA-PKcs controls global splicing and, via RBMX, regulates the maturation of AR-V and AR-FL transcripts. Ultimately, our data indicate that targeting DNA-PKcs attenuates AR-V signaling and provide evidence that DNA-PKcs blockade is an effective therapeutic option in advanced AR-V-positive patients with PC.
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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.