{
  "abstract": "Cell cycle dysregulation is a hallmark of cancer; however, tumors retaining homologous recombination (HR)-proficiency remain a major challenge. Although PARP inhibitors effectively target HR-deficient cancers, targeted therapies for BRCA1/2-wild-type, HR-proficient tumors are limited. High-grade serous ovarian cancer, approximately half of which is HR-proficient, illustrates that HR proficiency, together with replication stress and checkpoint dependence, may represent both a mechanism of therapeutic resistance and a druggable dependency on checkpoint-coupled DNA repair. This review synthesizes evidence that targeting either PLK1 or WEE1 independently exposes this vulnerability. PLK1 and WEE1 inhibition engage distinct mechanisms: PLK1 inhibition disrupts spindle assembly and HR competence, whereas WEE1 inhibition amplifies replication stress and forces premature mitotic entry. Nevertheless, both ultimately converge to compromise HR-associated repair, promote unresolved DNA damage, and trigger lethal mitotic catastrophe. Finally, we discuss biomarker-unselected trial failures, functional and replication stress-based patient stratification, and rational combinations with DNA-damaging agents and immunotherapy.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Integrative Genomics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan",
    "Department of Gynecological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China",
    "Next-Generation Precision Medicine Development Laboratory, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan",
    "Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan",
    "Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan",
    "Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Qian Xi",
      "orcid": "0009-0008-6436-5515"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Akiko Kunita",
      "orcid": "0009-0008-9989-8258"
    },
    {
      "affs": [
        4
      ],
      "name": "Saeko Nagai",
      "orcid": "0009-0006-3686-7134"
    },
    {
      "affs": [
        4
      ],
      "name": "Anh Quynh Duong",
      "orcid": "0009-0002-4143-4465"
    },
    {
      "affs": [
        5
      ],
      "name": "Masanori Kawakami",
      "orcid": "0000-0003-0207-7434"
    },
    {
      "affs": [
        0
      ],
      "name": "Katsutoshi Oda",
      "orcid": "0000-0002-2468-9573"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4s1gx9hvb6c98.bib",
  "cited_by": 0,
  "doi": "10.1080/15384101.2026.2751743",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13733244/",
  "id": "4s1gx9hvb6c98",
  "issns": [
    "1538-4101",
    "1551-4005"
  ],
  "landing_url": "https://doi.org/10.1080/15384101.2026.2751743",
  "language": "en",
  "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": [
    [
      "heading",
      "Review Article"
    ],
    [
      "openalex",
      "2730|PARP inhibition in cancer therapy"
    ]
  ],
  "openalex": "W7224083191",
  "pdf_url": "https://www.tandfonline.com/doi/pdf/10.1080/15384101.2026.2751743?needAccess=true",
  "pmcid": "PMC13733244",
  "pmid": "42947311",
  "published": "2026-10-27",
  "publisher": "Taylor & Francis",
  "ris": "https://research.draconitic.com/paper/4s1gx9hvb6c98.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:23:05Z",
      "native_id": "PMC13733244",
      "source": "pmc",
      "url": "https://doi.org/10.1080/15384101.2026.2751743"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|PARP inhibition in cancer therapy",
      "subfield": "oncology"
    }
  ],
  "title": "Targeting G2/M checkpoint vulnerability in homologous recombination-proficient tumors: lessons from ovarian cancer models",
  "title_text": "Targeting G2/M checkpoint vulnerability in homologous recombination-proficient tumors: lessons from ovarian cancer models",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:23:05Z",
  "url": "https://research.draconitic.com/paper/4s1gx9hvb6c98",
  "venue": "Cell Cycle",
  "versions": []
}