{
  "abstract": "This study investigates the transcriptional impact of Q901, a highly selective CDK7 inhibitor in clinical development. Q901 primarily disrupted MYC and E2F-dependent transcription program, downregulating cell cycle control and DNA damage repair pathways. CDK7 binding at the promoter-proximal regions was dramatically stabilized by Q901, leading to reduced occupancy of MYC, E2F, and RNA Polymerase II (RNAPII). These findings offered a novel therapeutic strategy to enhance cancer susceptibility to TOP1-DNA protein crosslinks (TOP1-DPCs) induced by TOP1 inhibitors. Resistance to TOP1 inhibitors arises through activation of DNA repair pathway when elongating RNAPII encounters TOP1-DPCs. By suppressing RNAPII transition from initiation to elongation and DNA repair pathways, Q901 stabilizes TOP1-DPCs and sensitizes tumor to TOP1 inhibitors. Preclinical studies demonstrated enhanced tumor suppression when combining Q901 with TOP1 inhibitor-based antibody-drug conjugates (TOP1i-ADCs), highlighting its potential as a therapeutic option for cancers resistant to TOP1i-ADC therapy.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, Korea.",
    "Qurient Co. Ltd., C801, 242 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 13487, Korea.",
    "University of Maryland Marlene & Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.",
    "Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA."
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Hyerim Jung",
      "orcid": "0009-0000-9270-9073"
    },
    {
      "affs": [
        1
      ],
      "name": "Yoonji Lee",
      "orcid": "0009-0001-6381-2570"
    },
    {
      "affs": [
        1
      ],
      "name": "Donghoon Yu"
    },
    {
      "affs": [
        1
      ],
      "name": "Yeejin Jeon",
      "orcid": "0000-0002-8413-4406"
    },
    {
      "affs": [
        1
      ],
      "name": "Hwankyu Kang"
    },
    {
      "affs": [
        0
      ],
      "name": "Dahun Um",
      "orcid": "0000-0002-7668-1629"
    },
    {
      "affs": [
        1
      ],
      "name": "Mooyoung Seo",
      "orcid": "0000-0001-6782-0490"
    },
    {
      "affs": [
        1
      ],
      "name": "Dongsik Park",
      "orcid": "0009-0001-4877-2726"
    },
    {
      "affs": [
        1
      ],
      "name": "Jeongjun Kim"
    },
    {
      "affs": [
        1
      ],
      "name": "Seung-Joo Lee",
      "orcid": "0009-0004-6616-4881"
    },
    {
      "affs": [
        1
      ],
      "name": "Jaeseung Kim",
      "orcid": "0009-0003-5816-7890"
    },
    {
      "affs": [
        2
      ],
      "name": "Lauren Escobedo"
    },
    {
      "affs": [
        2
      ],
      "name": "Yilun Sun",
      "orcid": "0000-0002-6249-2704"
    },
    {
      "affs": [
        3
      ],
      "name": "Anish Thomas",
      "orcid": "0000-0003-3293-3115"
    },
    {
      "affs": [
        1
      ],
      "name": "Kiyean Nam",
      "orcid": "0009-0008-5722-9224"
    },
    {
      "affs": [
        0
      ],
      "name": "Tae-Kyung Kim",
      "orcid": "0000-0001-5161-9864"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4wmdt68nd6z2e.bib",
  "cited_by": 1,
  "doi": "10.1126/sciadv.aeb4023",
  "fulltext_url": null,
  "id": "4wmdt68nd6z2e",
  "issns": [
    "2375-2548"
  ],
  "landing_url": "https://www.science.org/doi/10.1126/sciadv.aeb4023",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Cancer therapeutics and mechanisms"
    ]
  ],
  "openalex": "W7214952809",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-02",
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "ris": "https://research.draconitic.com/paper/4wmdt68nd6z2e.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:41Z",
      "native_id": "10.1126/sciadv.aeb4023",
      "source": "crossref",
      "url": "https://www.science.org/doi/10.1126/sciadv.aeb4023"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Cancer therapeutics and mechanisms",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Sensitizing tumor response to topoisomerase I antibody-drug conjugate by selective CDK7 inhibition",
  "title_text": "Sensitizing tumor response to topoisomerase I antibody-drug conjugate by selective CDK7 inhibition",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:41Z",
  "url": "https://research.draconitic.com/paper/4wmdt68nd6z2e",
  "venue": "Science Advances",
  "versions": []
}