{
  "abstract": "Prostate cancer (PCa) remains a leading cause of cancer-related mortality in men, with resistance to androgen-deprivation therapy (ADT) being the major clinical challenge. A key driver of this resistance is transcriptional reprogramming, during which androgen receptor (AR) activity shifts from ligand-dependent signaling to reactivation via splice variants such as AR-V7 and eventually to AR-negative states. The oncogene c-MYC plays a pivotal role through context-dependent crosstalk with AR, suppressing canonical AR-dependent transcription while promoting its own oncogenic program. This reprogramming is sustained by dysregulation of RB1/E2F, NF-κB, PI3K/AKT/mTOR, WNT/β-catenin, and Hippo/YAP/TAZ pathways, alongside N-MYC and L-MYC activation, forming an interconnected network driving phenotypic plasticity. This review focuses on cyclin-dependent kinases 8 and 19 (CDK8/19), components of the Mediator complex kinase module, as potential regulators of epigenetic plasticity in PCa capable of modulating both AR-dependent and AR-independent transcription. Preclinical studies show that CDK8/19 inhibition suppresses castration-resistant prostate cancer (CRPC) xenograft growth, restores ADT sensitivity, and additively enhances enzalutamide even in AR-V7-expressing resistant models, though the mechanisms of CDK8/19-mediated AR regulation remain largely undefined. We analyze the signaling pathways driving AR activity changes during PCa progression, evaluate potential mechanisms of CDK8/19-mediated AR regulation, and assess the therapeutic potential of CDK8/19 inhibitors with ADT.",
  "abstract_shown": true,
  "affiliations": [
    "Translational Medicine Research Center, Sirius University of Science and Technology, 1 Olympic Avenue, 354340 Sochi, Russia",
    "Institute of Experimental Oncology and Carcinogenesis, Blokhin National Medical Research Center of Oncology, 24 Kashirskoye Shosse, 115522 Moscow, Russia"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Maria Dodina",
      "orcid": "0009-0008-7506-0565"
    },
    {
      "affs": [
        0
      ],
      "name": "Polina Pavlova",
      "orcid": "0009-0005-2525-1361"
    },
    {
      "affs": [
        0
      ],
      "name": "Polina Kuzkokova",
      "orcid": "0009-0005-6865-6991"
    },
    {
      "affs": [
        0
      ],
      "name": "Aleksey Krasnyi"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Alexander Shtil"
    },
    {
      "affs": [
        0
      ],
      "name": "Roman Ivanov",
      "orcid": "0000-0002-9573-4183"
    },
    {
      "affs": [
        0
      ],
      "name": "Ekaterina Minskaia",
      "orcid": "0000-0002-1137-373X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f1096aqc20kjx.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27219855",
  "fulltext_url": null,
  "id": "f1096aqc20kjx",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/21/9855",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-03",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/f1096aqc20kjx.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T00:20:58Z",
      "native_id": "10.3390/ijms27219855",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/21/9855"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "issn:1422-0067",
      "subfield": "general"
    }
  ],
  "title": "Transcriptional Reprogramming in Prostate Cancer: Altered AR Activity, the Modulatory Role of CDK8/19, and Prospects for Combination Therapy",
  "title_text": "Transcriptional Reprogramming in Prostate Cancer: Altered AR Activity, the Modulatory Role of CDK8/19, and Prospects for Combination Therapy",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T00:21:14Z",
  "url": "https://research.draconitic.com/paper/f1096aqc20kjx",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}